The retina is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which translates that image into electrical neural impulses to the brain to create visual perception, the retina serving much the same function as the film or image sensor in a camera.
The neural retina consists of several layers of neurons interconnected by synapses, and is supported by an outer layer of pigmented epithelial cells. The primary light-sensing cells in the retina are the photoreceptor cells, which are of two types: rods and cones. Rods function mainly in dim light and provide black-and-white vision. Cones function in well-lit conditions and are responsible for the perception of colour, as well as high-acuity vision used for tasks such as reading. A third type of light-sensing cell, the photosensitive ganglion cell, is important for entrainment of circadian rhythms and reflexive responses such as the pupillary light reflex.
Light striking the retina initiates a cascade of chemical and electrical events that ultimately trigger nerve impulses that are sent to various visual centres of the brain through the fibres of the optic nerve. Neural signals from the rods and cones undergo processing by other neurons, whose output takes the form of action potentials in retinal ganglion cells whose axons form the optic nerve. Several important features of visual perception can be traced to the retinal encoding and processing of light.
In vertebrate embryonic development, the retina and the optic nerve originate as outgrowths of the developing brain, specifically the embryonic diencephalon; thus, the retina is considered part of the central nervous system (CNS) and is actually brain tissue. It is the only part of the CNS that can be visualized non-invasively.
Right human eye cross-sectional view; eyes vary significantly among animals.
pl. retinae /-ni/
|Artery||Central retinal artery|
The vertebrate retina is inverted in the sense that the light sensing cells are in back of the retina, so that light has to pass through layers of neurons and capillaries before it reaches the rods and cones. The ganglion cells, whose axons form the optic nerve, are at the front of the retina; therefore the optic nerve must cross through the retina en route to the brain. In this region there are no photoreceptors, giving rise to the blind spot. In contrast, in the cephalopod retina the photoreceptors are in front, with processing neurons and capillaries behind them. Because of this, cephalopods do not have a blind spot.
Although the overlying neural tissue is partly transparent, and the accompanying glial cells have been shown to act as fibre-optic channels to transport photons directly to the photoreceptors, light scattering does occur. Some vertebrates, including humans, have an area of the central retina adapted for high-acuity vision. This area, termed the fovea centralis, is avascular (does not have blood vessels), and has minimal neural tissue in front of the photoreceptors, thereby minimizing light scattering.
The cephalopods have a non-inverted retina which is comparable in resolving power to the eyes of many vertebrates. Squid eyes do not have an analog of the vertebrate retinal pigment epithelium (RPE). Although their photoreceptors contain a protein, retinochrome, that recycles retinal and replicates one of the functions of the vertebrate RPE, one could argue that cephalopod photoreceptors are not maintained as well as in vertebrates and that, as a result, the useful lifetime of photoreceptors in invertebrates is much shorter than in vertebrates. Having easily replaced stalk-eyes (some lobsters) or retinae (some spiders, such as Deinopis) rarely occurs.
The cephalopod retina does not originate as an outgrowth of the brain, as the vertebrate one does. It is arguable that this difference shows that vertebrate and cephalopod eyes are not homologous but have evolved separately. From an evolutionary perspective, a more complex structure such as the inverted retina can generally come about as a consequence of two alternate processes: (a) an advantageous "good" compromise between competing functional limitations, or (b) as a historical maladaptive relic of the convoluted path of organ evolution and transformation. Vision is an important adaptation in higher vertebrates.
A third view of the "inverted" vertebrate eye is that it combines two benefits: the maintenance of the photoreceptors mentioned above, and the reduction in light intensity necessary to avoid blinding the photoreceptors, which are based on the extremely sensitive eyes of the ancestors of modern hagfishes (a fish that lives in very deep, dark water).
The vertebrate retina has ten distinct layers. From closest to farthest from the vitreous body:
These layers can be grouped into 4 main processing stages: photoreception; transmission to bipolar cells; transmission to ganglion cells, which also contain photoreceptors, the photosensitive ganglion cells; and transmission along the optic nerve. At each synaptic stage there are also laterally connecting horizontal and amacrine cells.
The optic nerve is a central tract of many axons of ganglion cells connecting primarily to the lateral geniculate body, a visual relay station in the diencephalon (the rear of the forebrain). It also projects to the superior colliculus, the suprachiasmatic nucleus, and the nucleus of the optic tract. It passes through the other layers, creating the optic disc in primates.
Additional structures, not directly associated with vision, are found as outgrowths of the retina in some vertebrate groups. In birds, the pecten is a vascular structure of complex shape that projects from the retina into the vitreous humour; it supplies oxygen and nutrients to the eye, and may also aid in vision. Reptiles have a similar, but much simpler, structure.
In adult humans, the entire retina is approximately 72% of a sphere about 22 mm in diameter. The entire retina contains about 7 million cones and 75 to 150 million rods. The optic disc, a part of the retina sometimes called "the blind spot" because it lacks photoreceptors, is located at the optic papilla, where the optic-nerve fibres leave the eye. It appears as an oval white area of 3 mm². Temporal (in the direction of the temples) to this disc is the macula, at whose centre is the fovea, a pit that is responsible for our sharp central vision but is actually less sensitive to light because of its lack of rods. Human and non-human primates possess one fovea, as opposed to certain bird species, such as hawks, who are bifoviate, and dogs and cats, who possess no fovea but a central band known as the visual streak. Around the fovea extends the central retina for about 6 mm and then the peripheral retina. The farthest edge of the retina is defined by the ora serrata. The distance from one ora to the other (or macula), the most sensitive area along the horizontal meridian is about 32 mm.
In section, the retina is no more than 0.5 mm thick. It has three layers of nerve cells and two of synapses, including the unique ribbon synapse. The optic nerve carries the ganglion cell axons to the brain, and the blood vessels that supply the retina. The ganglion cells lie innermost in the eye while the photoreceptive cells lie beyond. Because of this counter-intuitive arrangement, light must first pass through and around the ganglion cells and through the thickness of the retina, (including its capillary vessels, not shown) before reaching the rods and cones. Light is absorbed by the retinal pigment epithelium or the choroid (both of which are opaque).
The white blood cells in the capillaries in front of the photoreceptors can be perceived as tiny bright moving dots when looking into blue light. This is known as the blue field entoptic phenomenon (or Scheerer's phenomenon).
Between the ganglion cell layer and the rods and cones there are two layers of neuropils where synaptic contacts are made. The neuropil layers are the outer plexiform layer and the inner plexiform layer. In the outer neuropil layer, the rods and cones connect to the vertically running bipolar cells, and the horizontally oriented horizontal cells connect to ganglion cells.
The central retina predominantly contains cones, while the peripheral retina predominantly contains rods. In total, there are about seven million cones and a hundred million rods. At the centre of the macula is the foveal pit where the cones are narrow and long, and, arranged in a hexagonal mosaic, the most dense. At the foveal pit the other retinal layers are displaced, before building up along the foveal slope until the rim of the fovea, or parafovea, is reached, which is the thickest portion of the retina. The macula has a yellow pigmentation, from screening pigments, and is known as the macula lutea. The area directly surrounding the fovea has the highest density of rods converging on single bipolar cells. Since its cones have a much lesser convergence of signals, the fovea allows for the sharpest vision the eye can attain.
Though the rod and cones are a mosaic of sorts, transmission from receptors, to bipolars, to ganglion cells is not direct. Since there are about 150 million receptors and only 1 million optic nerve fibres, there must be convergence and thus mixing of signals. Moreover, the horizontal action of the horizontal and amacrine cells can allow one area of the retina to control another (e.g. one stimulus inhibiting another). This inhibition is key to lessening the sum of messages sent to the higher regions of the brain. In some lower vertebrates (e.g. the pigeon), there is a "centrifugal" control of messages – that is, one layer can control another, or higher regions of the brain can drive the retinal nerve cells, but in primates this does not occur.
From innermost to outermost, the layers identifiable by OCT are as follows:
|#||OCT Layer / Conventional Label||Anatomical Correlate||Reflectivity||Specific
|1||Posterior cortical vitreous||Posterior cortical vitreous||Hyper-reflective||Yes|||
|2||Preretinal space||In eyes where the vitreous has fully or partially detached from the retina, this is the space created between the posterior cortical vitreous face and the internal limiting membrane of the retina.||Hypo-reflective|||
|3||Internal limiting membrane (ILM)||Formed by Müller cell endfeet
(unclear if it can be observed on OCT)
|Nerve fiber layer (NFL)||Ganglion cell axons travelling towards the optic nerve|
|4||Ganglion cell layer (GCL)||Ganglion cell bodies (and some displaced amacrine cells)||Hypo-reflective|||
|5||Inner plexiform layer (IPL)||Synapses between bipolar, amacrine and ganglion cells||Hyper-reflective|||
|6||Inner nuclear layer (INL)||a) Horizontal, bipolar and amacrine cell bodies
b) Müller cell nuclei
|7||Outer plexiform layer (OPL)||Synapses between photoreceptor, bipolar and horizontal cells||Hyper-reflective|||
|8||(Inner half) Henle’s nerve fiber layer (HL)||Photoreceptor axons
(obliquely orientated fibres; not present in mid-peripheral or peripheral retina)
|(Outer half) Outer nuclear layer (ONL)||The photoreceptor cell bodies|
|9||External limiting membrane (ELM)||Made of zonulae adherens between Müller cells and photoreceptor inner segments||Hyper-reflective|||
|10||Myoid zone (MZ)||The innermost portion of the photoreceptor inner segment (IS) containing:||Hypo-reflective||No|||
|11||Ellipsoid zone (EZ)||The outermost portion of the photoreceptor inner segment (IS) packed with mitochondria||Very Hyper-reflective||No|||
|IS/OS junction or Photoreceptor integrity line (PIL)||The photoreceptor connecting cilia which bridge the inner and outer segments of the photoreceptor cells.|
|12||Photoreceptor outer segments (OS)||The photoreceptor outer segments (OS) which contain disks filled with opsin, the molecule that absorbs photons.||Hypo-reflective|||
|13||Interdigitation zone (IZ)||Apices of the RPE cells which encase part of the cone OSs.
Poorly distinguishable from RPE. Previously: "cone outer segment tips line" (COST)
|14||RPE/Bruch’s complex||RPE phagosome zone||Very Hyper-reflective||No|||
|RPE melanosome zone||Hypo-reflective|
|RPE mitochondria zone + Junction between the RPE & Bruch's membrane||Very Hyper-reflective|
|15||Choriocapillaris||Thin layer of moderate reflectivity in inner choroid||No|||
|16||Sattler’s layer||Thick layer of round or ovalshaped hyperreflective profiles, with hyporeflective cores in mid-choroid|||
|17||Haller’s layer||Thick layer of oval-shaped hyperreflective profiles, with hyporeflective cores in outer choroid|||
|18||Choroidal-scleral juncture||Zone at the outer choroid with a marked change in texture, in which large circular or ovoid profiles abut a
homogenous region of variable reflectivity
Retinal development begins with the establishment of the eye fields mediated by the SHH and SIX3 proteins, with subsequent development of the optic vesicles regulated by the PAX6 and LHX2 proteins. The role of Pax6 in eye development was elegantly demonstrated by Walter Gehring and colleagues, who showed that ectopic expression of Pax6 can lead to eye formation on Drosophila antennae, wings, and legs. The optic vesicle gives rise to three structures: the neural retina, the retinal pigmented epithelium, and the optic stalk. The neural retina contains the retinal progenitor cells (RPCs) that give rise to the seven cell types of the retina. Differentiation begins with the retinal ganglion cells and concludes with production of the Muller glia. Although each cell type differentiates from the RPCs in a sequential order, there is considerable overlap in the timing of when individual cell types differentiate. The cues that determine a RPC daughter cell fate are coded by multiple transcription factor families including the bHLH and homeodomain factors.
In addition to guiding cell fate determination, cues exist in the retina to determine the dorsal-ventral (D-V) and nasal-temporal (N-T) axes. The D-V axis is established by a ventral to dorsal gradient of VAX2, whereas the N-T axis is coordinated by expression of the forkhead transcription factors FOXD1 and FOXG1. Additional gradients are formed within the retina that aid in proper targeting of RGC axons that function to establish the retinotopic map.
The retina is stratified into distinct layers, each containing specific cell types or cellular compartments that have metabolisms with different nutritional requirements. To satisfy these requirements, the ophthalmic artery bifurcates and supplies the retina via two distinct vascular networks: the choroidal network, which supplies the choroid and the outer retina, and the retinal network, which supplies the retina's inner layer.
At first glance, one may think that the vertebrate retina is "wired wrongly" or "badly designed"; but in fact, the retina could not function if it were not inverted. The photoreceptor layer must be embedded in the retinal pigment epithelium (RPE), which performs at least seven vital functions, one of the most obvious being to supply oxygen and other necessary nutrients needed for the photoreceptors to function. These nutrients include glucose, fatty acids, and retinal. The mammalian photoreceptor amplification process uses large quantities energy for vision in photopic conditions (requiring less under scotopic conditions) and, thus, requires the large supply nutrients supplied by the blood vessels in the choroid, which lies beyond the RPE. The choroid supplies about 75% of these nutrients to the retina and the retinal vasculature only 25%.
When light strikes 11-cis-retinal (in the disks in the rods and cones), 11-cis-retinal changes to all-trans-retinal which then triggers changes in the opsins. Now, the outer segments do not regenerate the retinal back into the cis- form once it has been changed by light. Instead the retinal is pumped out to the surrounding RPE where it is regenerated and transported back into the outer segments of the photoreceptors. This recycling function of the RPE protects the photoreceptors against photo-oxidative damage and allows the photoreceptor cells to have decades-long useful lives.
The bird retina is devoid of blood vessels, perhaps to give unobscured passage of light for forming images, thus giving better resolution. It is, therefore, a considered view that the bird retina depends for nutrition and oxygen supply on a specialized organ, called the "pecten" or pecten oculi, located on the blind spot or optic disk. This organ is extremely rich in blood vessels and is thought to supply nutrition and oxygen to the bird retina by diffusion through the vitreous body. The pecten is highly rich in alkaline phosphatase activity and polarized cells in its bridge portion – both befitting its secretory role. Pecten cells are packed with dark melanin granules, which have been theorized to keep this organ warm with the absorption of stray light falling on the pecten. This is considered to enhance metabolic rate of the pecten, thereby exporting more nutritive molecules to meet the stringent energy requirements of the retina during long periods of exposure to light.
The bifurcations and other physical characteristics of the inner retinal vascular network are known to vary among individuals, and these individual variances have been used for biometric identification and for early detection of the onset of disease. The mapping of vascular bifurcations is one of the basic steps in biometric identification. Results of such analyses of retinal blood vessel structure can be evaluated against the ground truth data of vascular bifurcations of retinal fundus images that are obtained from the DRIVE dataset. In addition, the classes of vessels of the DRIVE dataset have also been identified, and an automated method for accurate extraction of these bifurcations is also available. Changes in retinal blood circulation are seen with aging and exposure to air pollution, and may indicate cardiovascular diseases such as hypertension and atherosclerosis. Determining the equivalent width of arterioles and venules near the optic disc is also a widely used technique to identify cardiovascular risks.
The retina translates an optical image into neural impulses by the patterned excitation of the colour-sensitive pigments of its rods and cones, the retina's photoreceptor cells. The excitation is processed by the neural system and various parts of the brain working in parallel to form a representation of the external environment in the brain.
The cones respond to bright light and mediate high-resolution colour vision during daylight illumination (also called photopic vision). The rods are saturated at daylight levels and don't contribute to pattern vision. However, rods do respond to dim light and mediate lower-resolution, monochromatic vision under very low levels of illumination (called scotopic vision). The illumination in most office settings falls between these two levels and is called mesopic vision. At mesopic light levels, both the rods and cones are actively contributing pattern information. What contribution the rod information makes to pattern vision under these circumstances is unclear.
The response of cones to various wavelengths of light is called their spectral sensitivity. In normal human vision, the spectral sensitivity of a cone falls into one of three subtypes, often called blue, green, or red but more accurately known as short, medium, or long wavelength-sensitive cone subtypes. It is a lack of one or more of the cone subtypes that causes individuals to have deficiencies in colour vision or various kinds of colour blindness. These individuals are not blind to objects of a particular colour but are unable to distinguish between colours that can be distinguished by people with normal vision. Humans have this trichromatic vision, while most other mammals lack cones with red sensitive pigment and therefore have poorer dichromatic colour vision. However, some animals have four spectral subtypes, e.g. the trout adds an ultraviolet subgroup to short, medium, and long subtypes that are similar to humans. Some fish are sensitive to the polarization of light as well.
In the photoreceptors, exposure to light hyperpolarizes the membrane in a series of graded shifts. The outer cell segment contains a photopigment. Inside the cell the normal levels of cyclic guanosine monophosphate (cGMP) keep the Na+ channel open, and thus in the resting state the cell is depolarised. The photon causes the retinal bound to the receptor protein to isomerise to trans-retinal. This causes the receptor to activate multiple G-proteins. This in turn causes the Ga-subunit of the protein to activate a phosphodiesterase (PDE6), which degrades cGMP, resulting in the closing of Na+ cyclic nucleotide-gated ion channels (CNGs). Thus the cell is hyperpolarised. The amount of neurotransmitter released is reduced in bright light and increases as light levels fall. The actual photopigment is bleached away in bright light and only replaced as a chemical process, so in a transition from bright light to darkness the eye can take up to thirty minutes to reach full sensitivity.
When thus excited by light, the photoceptor sends a proportional response synaptically to bipolar cells which in turn signal the retinal ganglion cells. The photoreceptors are also cross-linked by horizontal cells and amacrine cells, which modify the synaptic signal before it reaches the ganglion cells, the neural signals being intermixed and combined. Of the retina's nerve cells, only the retinal ganglion cells and few amacrine cells create action potentials.
In the retinal ganglion cells there are two types of response, depending on the receptive field of the cell. The receptive fields of retinal ganglion cells comprise a central, approximately circular area, where light has one effect on the firing of the cell, and an annular surround, where light has the opposite effect. In ON cells, an increment in light intensity in the centre of the receptive field causes the firing rate to increase. In OFF cells, it makes it decrease. In a linear model, this response profile is well described by a difference of Gaussians and is the basis for edge detection algorithms. Beyond this simple difference, ganglion cells are also differentiated by chromatic sensitivity and the type of spatial summation. Cells showing linear spatial summation are termed X cells (also called parvocellular, P, or midget ganglion cells), and those showing non-linear summation are Y cells (also called magnocellular, M, or parasol retinal ganglion cells), although the correspondence between X and Y cells (in the cat retina) and P and M cells (in the primate retina) is not as simple as it once seemed.
In the transfer of visual signals to the brain, the visual pathway, the retina is vertically divided in two, a temporal (nearer to the temple) half and a nasal (nearer to the nose) half. The axons from the nasal half cross the brain at the optic chiasma to join with axons from the temporal half of the other eye before passing into the lateral geniculate body.
Although there are more than 130 million retinal receptors, there are only approximately 1.2 million fibres (axons) in the optic nerve. So, a large amount of pre-processing is performed within the retina. The fovea produces the most accurate information. Despite occupying about 0.01% of the visual field (less than 2° of visual angle), about 10% of axons in the optic nerve are devoted to the fovea. The resolution limit of the fovea has been determined to be around 10,000 points. The information capacity is estimated at 500,000 bits per second (for more information on bits, see information theory) without colour or around 600,000 bits per second including colour.
When the retina sends neural impulses representing an image to the brain, it spatially encodes (compresses) those impulses to fit the limited capacity of the optic nerve. Compression is necessary because there are 100 times more photoreceptor cells than ganglion cells. This is done by "decorrelation", which is carried out by the "centre–surround structures", which are implemented by the bipolar and ganglion cells.
There are two types of centre–surround structures in the retina – on-centres and off-centres. On-centres have a positively weighted centre and a negatively weighted surround. Off-centres are just the opposite. Positive weighting is more commonly known as excitatory, and negative weighting as inhibitory.
These centre–surround structures are not physical apparent, in the sense that one cannot see them by staining samples of tissue and examining the retina's anatomy. The centre–surround structures are logical (i.e., mathematically abstract) in the sense that they depend on the connection strengths between bipolar and ganglion cells. It is believed that the connection strengths between cells is caused by the number and types of ion channels embedded in the synapses between the bipolar and ganglion cells.
The centre–surround structures are mathematically equivalent to the edge detection algorithms used by computer programmers to extract or enhance the edges in a digital photograph. Thus, the retina performs operations on the image-representing impulses to enhance the edges of objects within its visual field. For example, in a picture of a dog, a cat and a car, it is the edges of these objects that contain the most information. In order for higher functions in the brain (or in a computer for that matter) to extract and classify objects such as a dog and a cat, the retina is the first step to separating out the various objects within the scene.
As an example, the following matrix is at the heart of a computer algorithm that implements edge detection. This matrix is the computer equivalent to the centre–surround structure. In this example, each box (element) within this matrix would be connected to one photoreceptor. The photoreceptor in the centre is the current receptor being processed. The centre photoreceptor is multiplied by the +1 weight factor. The surrounding photoreceptors are the "nearest neighbors" to the centre and are multiplied by the -1/8 value. The sum of all nine of these elements is finally calculated. This summation is repeated for every photoreceptor in the image by shifting left to the end of a row and then down to the next line.
The total sum of this matrix is zero, if all the inputs from the nine photoreceptors are of the same value. The zero result indicates the image was uniform (non-changing) within this small patch. Negative or positive sums mean the image was varying (changing) within this small patch of nine photoreceptors.
The above matrix is only an approximation to what really happens inside the retina. The differences are:
Here is an example of an input image and how edge detection would modify it.
Once the image is spatially encoded by the centre–surround structures, the signal is sent out along the optic nerve (via the axons of the ganglion cells) through the optic chiasm to the LGN (lateral geniculate nucleus). The exact function of the LGN is unknown at this time. The output of the LGN is then sent to the back of the brain. Specifically, the output of the LGN "radiates" out to the V1 primary visual cortex.
Simplified signal flow: Photoreceptors → Bipolar → Ganglion → Chiasm → LGN → V1 cortex
There are many inherited and acquired diseases or disorders that may affect the retina. Some of them include:
A number of different instruments are available for the diagnosis of diseases and disorders affecting the retina. Ophthalmoscopy and fundus photography have long been used to examine the retina. Recently, adaptive optics has been used to image individual rods and cones in the living human retina, and a company based in Scotland has engineered technology that allows physicians to observe the complete retina without any discomfort to patients.
The electroretinogram is used to non-invasively measure the retina's electrical activity, which is affected by certain diseases. A relatively new technology, now becoming widely available, is optical coherence tomography (OCT). This non-invasive technique allows one to obtain a 3D volumetric or high resolution cross-sectional tomogram of the fine structures of the retina, with histologic quality.
Treatment depends upon the nature of the disease or disorder.
The following are commonly modalities of management for retinal disease:
Rare or uncommon methods of treatment for retinal disease
Retinal gene therapy
Gene therapy holds promise as a potential avenue to cure a wide range of retinal diseases. This involves using a non-infectious virus to shuttle a gene into a part of the retina. Recombinant adeno-associated virus (rAAV) vectors possess a number of features that render them ideally suited for retinal gene therapy, including a lack of pathogenicity, minimal immunogenicity, and the ability to transduce postmitotic cells in a stable and efficient manner. rAAV vectors are increasingly utilized for their ability to mediate efficient transduction of retinal pigment epithelium (RPE), photoreceptor cells and retinal ganglion cells. Each cell type can be specifically targeted by choosing the appropriate combination of AAV serotype, promoter, and intraocular injection site.
Several clinical trials have already reported positive results using rAAV to treat Leber's congenital amaurosis, showing that the therapy was both safe and effective. There were no serious adverse events, and patients in all three studies showed improvement in their visual function as measured by a number of methods. The methods used varied among the three trials, but included both functional methods such as visual acuity and functional mobility as well as objective measures that are less susceptible to bias, such as the pupil's ability to respond to light and improvements on functional MRI. Improvements were sustained over the long-term, with patients continuing to do well after more than 1.5 years.
The unique architecture of the retina and its relatively immune-privileged environment help this process. Tight junctions that form the blood retinal barrier separate the subretinal space from the blood supply, thus protecting it from microbes and most immune-mediated damage, and enhancing its potential to respond to vector-mediated therapies. The highly compartmentalized anatomy of the eye facilitates accurate delivery of therapeutic vector suspensions to specific tissues under direct visualization using microsurgical techniques. In the sheltered environment of the retina, AAV vectors are able to maintain high levels of transgene expression in the retinal pigmented epithelium (RPE), photoreceptors, or ganglion cells for long periods of time after a single treatment. In addition, the eye and the visual system can be routinely and easily monitored for visual function and retinal structural changes after injections with noninvasive advanced technology, such as visual acuities, contrast sensitivity, fundus auto-fluorescence (FAF), dark-adapted visual thresholds, vascular diameters, pupillometry, electroretinography (ERG), multifocal ERG and optical coherence tomography (OCT).
This strategy is effective against a number of retinal diseases that have been studied, including neovascular diseases that are features of age-related macular degeneration, diabetic retinopathy and retinopathy of prematurity. Since the regulation of vascularization in the mature retina involves a balance between endogenous positive growth factors, such as vascular endothelial growth factor (VEGF) and inhibitors of angiogenesis, such as pigment epithelium-derived factor (PEDF), rAAV-mediated expression of PEDF, angiostatin, and the soluble VEGF receptor sFlt-1, which are all antiangiogenic proteins, have been shown to reduce aberrant vessel formation in animal models. Since specific gene therapies cannot readily be used to treat a significant fraction of patients with retinal dystrophy, there is a major interest in developing a more generally applicable survival factor therapy. Neurotrophic factors have the ability to modulate neuronal growth during development to maintain existing cells and to allow recovery of injured neuronal populations in the eye. AAV encoding neurotrophic factors such as fibroblast growth factor (FGF) family members and GDNF either protected photoreceptors from apoptosis or slowed down cell death.
Organ transplantation Transplantation of retinas has been attempted, but without much success. At MIT, The University of Southern California, RWTH Aachen University, and the University of New South Wales, an "artificial retina" is under development: an implant which will bypass the photoreceptors of the retina and stimulate the attached nerve cells directly, with signals from a digital camera.
A recent University of Pennsylvania study calculated that the approximate bandwidth of human retinas is 8.75 megabits per second, whereas a guinea pig's retinal transfer rate is 875 kilobits per second.
MacLaren & Pearson and colleagues at University College London and Moorfields Eye Hospital in London, in 2006, showed that photoreceptor cells could be transplanted successfully in the mouse retina if donor cells were at a critical developmental stage. Recently Ader and colleagues in Dublin showed, using the electron microscope, that transplanted photoreceptors formed synaptic connections.
In 2012, Sebastian Seung and his laboratory at MIT have launched EyeWire, an online Citizen science game where players trace neurons in the retina. The goals of the EyeWire project are to identify specific cell types within the known broad classes of retinal cells, and to map the connections between neurons in the retina, which will help to determine how vision works.
The central retinal artery (retinal artery) branches off the ophthalmic artery, running inferior to the optic nerve within its dural sheath to the eyeball.Cone cell
Cone cells, or cones, are photoreceptor cells in the retinas of vertebrate eyes (e.g. the human eye). They respond differently to light of different wavelengths, and are thus responsible for color vision and function best in relatively bright light, as opposed to rod cells, which work better in dim light. Cone cells are densely packed in the fovea centralis, a 0.3 mm diameter rod-free area with very thin, densely packed cones which quickly reduce in number towards the periphery of the retina. There are about six to seven million cones in a human eye and are most concentrated towards the macula.
The commonly cited figure of six million cone cells in the human eye was found by Osterberg in 1935. Oyster's textbook (1999) cites work by Curcio et al. (1990) indicating an average close to 4.5 million cone cells and 90 million rod cells in the human retina.Cones are less sensitive to light than the rod cells in the retina (which support vision at low light levels), but allow the perception of color. They are also able to perceive finer detail and more rapid changes in images, because their response times to stimuli are faster than those of rods. Cones are normally one of the three types, each with different pigment, namely: S-cones, M-cones and L-cones. Each cone is therefore sensitive to visible wavelengths of light that correspond to short-wavelength, medium-wavelength and long-wavelength light. Because humans usually have three kinds of cones with different photopsins, which have different response curves and thus respond to variation in color in different ways, we have trichromatic vision. Being color blind can change this, and there have been some verified reports of people with four or more types of cones, giving them tetrachromatic vision.
The three pigments responsible for detecting light have been shown to vary in their exact chemical composition due to genetic mutation; different individuals will have cones with different color sensitivity.Diabetic retinopathy
Diabetic retinopathy, also known as diabetic eye disease, is a medical condition in which damage occurs to the retina due to diabetes mellitus. It is a leading cause of blindness.Diabetic retinopathy affects up to 80 percent of those who have had diabetes for 20 years or more. At least 90% of new cases could be reduced with proper treatment and monitoring of the eyes. The longer a person has diabetes, the higher his or her chances of developing diabetic retinopathy. Each year in the United States, diabetic retinopathy accounts for 12% of all new cases of blindness. It is also the leading cause of blindness in people aged 20 to 64.Human eye
The human eye is an organ which reacts to light and pressure. As a sense organ, the mammalian eye allows vision. Human eyes help to provide a three dimensional, moving image, normally coloured in daylight. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth. The human eye can differentiate between about 10 million colors and is possibly capable of detecting a single photon.Similar to the eyes of other mammals, the human eye's non-image-forming photosensitive ganglion cells in the retina receive light signals which affect adjustment of the size of the pupil, regulation and suppression of the hormone melatonin and entrainment of the body clock.IMac (Intel-based)
The Intel-based iMac is a family of Macintosh desktop computers designed, manufactured and sold by Apple Inc. since 2006.
Pre-2009 iMac models featured either a white polycarbonate enclosure or an aluminium enclosure. The October 2009 iMac model featured a unibody aluminum enclosure, a version of which can still be seen on the current model. The current iMacs released since October 2012 also feature a much thinner display, with the edge measuring just 5 mm.IPad (4th generation)
The fourth-generation iPad (marketed as iPad with Retina display, colloquially referred to as the iPad 4) is a tablet computer produced and marketed by Apple Inc. Compared to its predecessor, the third-generation iPad, the fourth-generation iPad maintained the Retina Display but featured new and upgraded components such as the Apple A6X chip and the Lightning connector, which was introduced on September 12, 2012. It shipped with iOS 6.0, which provides a platform for audio-visual media, including electronic books, periodicals, films, music, computer games, presentations and web content. Like the iPad 2 and the third-generation iPad, it has been supported by five major iOS releases, in this case iOS 6, 7, 8, 9, and 10. iOS 11, which was released on 19 September 2017, does not have support for the fourth-generation iPad because iOS 11 drops support for all 32-bit devices.
It was announced at a media conference on October 23, 2012 as the fourth generation of the iPad line, and was first released on November 2, 2012, in 35 countries, and then through December in ten other countries including China, India and Brazil. The third generation was discontinued following the fourth's announcement, after only seven months of general availability.The device is available with either a black or white front glass panel and various connectivity and storage options. Storage size options include 16 GB, 32 GB, 64 GB, and 128 GB; the available connectivity options are Wi-Fi only and Wi-Fi + Cellular with LTE capabilities.
The fourth-generation iPad received primarily positive reviews and was praised for its hardware improvements as well as the Retina display, which was also featured in the device's predecessor. Furthermore, benchmarks reveal that the fourth-generation iPad is able to perform CPU-reliant tasks twice as fast as its predecessor. During the first weekend of sales, an aggregated amount of 3 million fourth-generation iPads and iPad Minis were sold.IPad Mini 2
The iPad Mini 2 (stylized and marketed as the iPad mini 2, previously marketed as the iPad mini with Retina display) is the second generation iPad Mini tablet computer produced and marketed by Apple Inc. It has a design almost identical to that of the first generation iPad Mini but features internal revisions such as the addition of the A7 system-on-a-chip and 2,048 × 1,536 resolution Retina Display. The iPad Mini 2 has nearly the same hardware as its larger sibling, the iPad Air. Apple released the iPad Mini 2 in Space Gray and Silver colors on November 12, 2013.
Its successor, the iPad Mini 3, was unveiled on October 16, 2014, featuring the same internals but adding Touch ID, differing storage sizes, and an additional gold color.
The iPad Mini 2 was discontinued on March 21, 2017, following the press announcement of a new, lower cost iPad, which replaces the iPad Air 2.
The iPad Mini 2 is the first iPad Mini to support six major versions of iOS, from iOS 7 through iOS 12.MacBook (2015–present)
The MacBook (known colloquially as the Retina MacBook or 12-inch MacBook) is a line of Macintosh portable computers introduced in March 2015 by Apple Inc. The MacBook has a similar appearance to the MacBook Air, but is thinner and lighter, and is available in colors called space gray, silver, gold, and rose gold. It offers a high-resolution Retina Display, a Force Touch trackpad, a redesigned keyboard, and only two ports: a headphone jack and a USB 3.1 Type-C port for charging, data transfer and video output.
In the MacBook product line, the MacBook sits below the MacBook Pro in terms of average specifications. Compared to the MacBook Air which at the time had 13.3-inch and 11.6-inch screen sizes, the 12-inch MacBook is considered a more premium device due to its higher resolution Retina Display, more compact form factor, the absence of fan, and higher storage and memory. However, the processor and graphic performance is inferior to the MacBook Air. Many reviewers have also criticized the shallow travel of the redesigned keyboard keys.On April 19, 2016, Apple updated the MacBook with new sixth-generation Intel Core M processors, Intel HD 515 graphics, faster RAM, longer battery life, faster storage and a new rose gold finish.On June 5, 2017, Apple again updated the MacBook with Intel Kaby Lake m3, i5, and i7 processors (previously known as m3, m5, and m7). It features the second generation butterfly switches which introduce new symbols for the control and option keys. The MacBook also features faster SSD storage and RAM.On October 30, 2018, Apple quietly eliminated two MacBook color options (rose gold and original gold) for one, new color option (new gold) to match the MacBook Air's 2018 color scheme. Aside from this, other technical specifications on the 2018 MacBook were not updated.MacBook Pro
The MacBook Pro (sometimes abbreviated as MBP) is a line of Macintosh portable computers introduced in January 2006 by Apple Inc. It is the high-end model of the MacBook family and is currently available in 13- and 15-inch screen sizes. A 17-inch version was available between April 2006 and June 2012.
The first generation MacBook Pro is externally similar to the PowerBook G4 it replaces, but uses Intel Core processors instead of PowerPC G4 chips. The 15-inch model was introduced first, in January 2006; the 17-inch model followed in April. Both received several updates and Core 2 Duo processors later in 2006.
The product's second iteration, known as the "unibody" model, has a casing made from a single piece of aluminum. It debuted in October 2008 in 13- and 15-inch screen sizes. In January 2009, the 17-inch model was updated with the same unibody design. Subsequent updates brought upgraded Intel Core i5 and i7 processors and introduced Intel's Thunderbolt technology.
Apple released the third generation of MacBook Pro with a 15-inch screen during WWDC 2012 and discontinued the 17-inch variant. The previous generation 13- and 15-inch unibody models continued to sell with updated processors. The third generation model is thinner than its predecessor and is the first to include a high-resolution Retina Display. A 13-inch variant was released in October 2012.
The fourth generation MacBook Pro was announced on October 27, 2016. This generation replaced all data ports with USB-C, and with the exception of the baseline model, replaced the function keys with an interactive touchscreen strip called the "Touch Bar" with a Touch ID sensor integrated into the Power button.Macula of retina
The macula or macula lutea is an oval-shaped pigmented area near the center of the retina of the human eye and some other animalian eyes. The macula in humans has a diameter of around 5.5 mm (0.22 in) and is subdivided into the umbo, foveola, foveal avascular zone, fovea, parafovea, and perifovea areas.The anatomical macula at 5.5 mm (0.22 in) is much larger than the clinical macula which, at 1.5 mm (0.059 in), corresponds to the anatomical fovea.The macula is responsible for the central, high-resolution, color vision that is possible in good light; and this kind of vision is impaired if the macula is damaged, for example in macular degeneration. The clinical macula is seen when viewed from the pupil, as in ophthalmoscopy or retinal photography.
The term macula lutea comes from Latin macula, "spot", and lutea, "yellow".Retina display
Retina display is a brand name used by Apple for its series of IPS LCD, and OLED displays that have a higher pixel density than traditional Apple displays. Apple has applied to register the term "Retina" as a trademark in regard to computers and mobile devices with the United States Patent and Trademark Office, Canadian Intellectual Property Office, and in Jamaica. On November 27, 2012 the US Patent and Trademark office approved Apple's application and "Retina" is now a registered trademark for computer equipment.
When an Apple product has a Retina display, each user interface widget is doubled in width and height to compensate for the smaller pixels. Apple calls this mode HiDPI mode. In simple words, it was one logical pixel = four physical pixels at the very beginning. The advantage of this equation is that the CPU "sees" a small portion of the data and calculates the relative positions of each element and GPU renders these elements with high quality assets to make the output much sharper and more clear. The goal of Retina displays is to make the display of text and images extremely crisp, so pixels are not visible to the naked eye. This allows displays to rival the smooth curves and sharpness of printed text and immediacy of photographic prints.These better quality displays have been gradually released over a number of years, and the term is now used for nearly all of Apple products containing a screen, including Apple Watch, iPhone, iPod Touch, iPad, MacBook, MacBook Air, MacBook Pro, and iMac. Apple uses slightly different versions of the term for these models, including Retina HD Display for iPhone 6 and later versions, and Retina 4K/5K Display for iMac.Apple's Retina displays are not an absolute standard but vary depending on the size of the display on the device, and how close the user would typically be viewing the screen. Where users view the screen at a closer distance to their eyes, as on smaller devices with smaller displays, the displays have more PPI (Pixels Per Inch), while larger devices with larger displays where the user views the screen further away use fewer PPI. Later device versions have had additional improvement, either counted by an increase in the screen size (the iPhone 6 Plus) and/or contrast ratio (the iPhone 6 Plus, and iMac with Retina 4K/5K Display), and/or more recently with PPI count (iPhone X, XR, XS, and XS Max), thus Apple using the name “Retina HD Display", "Retina 4K/5K Display", "Super Retina HD Display", or "Liquid Retina HD Display".Retinal detachment
Retinal detachment is a disorder of the eye in which the retina separates from the layer underneath. Symptoms include an increase in the number of floaters, flashes of light, and worsening of the outer part of the visual field. This may be described as a curtain over part of the field of vision. In about 7% of cases both eyes are affected. Without treatment permanent loss of vision may occur.The mechanism most commonly involves a break in the retina that then allows the fluid in the eye to get behind the retina. A break in the retina can occur from a posterior vitreous detachment, injury to the eye, or inflammation of the eye. Other risk factors include being short sighted and previous cataract surgery. Retinal detachments also rarely occur due to a choroidal tumor. Diagnosis is by either looking at the back of the eye with an ophthalmoscope or by ultrasound.In those with a retinal tear, efforts to prevent it becoming a detachment include cryotherapy using a cold probe or photocoagulation using a laser. Treatment of retinal detachment should be carried out in a timely manner. This may include scleral buckling where silicone is sutured to the outside of the eye, pneumatic retinopexy where gas is injected into the eye, or vitrectomy where the vitreous is partly removed and replaced with either gas or oil.Retinal detachments affect between 0.6 and 1.8 people per 10,000 per year. About 0.3% of people are affected at some point in their life. It is most common in people who are in their 60s or 70s. Males are more often affected than females. The long term outcomes depend on the duration of the detachment and whether the macula was detached. If treated before the macula detaches outcomes are generally good.Retinal ganglion cell
A retinal ganglion cell (RGC) is a type of neuron located near the inner surface (the ganglion cell layer) of the retina of the eye. It receives visual information from photoreceptors via two intermediate neuron types: bipolar cells and retina amacrine cells. Retina amacrine cells, particularly narrow field cells, are important for creating functional subunits within the ganglion cell layer and making it so that ganglion cells can observe a small dot moving a small distance. Retinal ganglion cells collectively transmit image-forming and non-image forming visual information from the retina in the form of action potential to several regions in the thalamus, hypothalamus, and mesencephalon, or midbrain.
Retinal ganglion cells vary significantly in terms of their size, connections, and responses to visual stimulation but they all share the defining property of having a long axon that extends into the brain. These axons form the optic nerve, optic chiasm, and optic tract.
A small percentage of retinal ganglion cells contribute little or nothing to vision, but are themselves photosensitive; their axons form the retinohypothalamic tract and contribute to circadian rhythms and pupillary light reflex, the resizing of the pupil.
The six types of retinal neurons are bipolar cells, ganglion cells, horizontal cells, retina amacrine cells, and rod and cone photoreceptors.Retinal homeobox protein Rx
Retinal homeobox protein Rx also known as retina and anterior neural fold homeobox is a protein that in humans is encoded by the RAX gene. The RAX gene is located on chromosome 18 in humans, mice, and rats.Retinal pigment epithelium
The pigmented layer of retina or retinal pigment epithelium (RPE) is the pigmented cell layer just outside the neurosensory retina that nourishes retinal visual cells, and is firmly attached to the underlying choroid and overlying retinal visual cells.Retinopathy
Retinopathy is any damage to the retina of the eyes, which may cause vision impairment. Retinopathy often refers to retinal vascular disease, or damage to the retina caused by abnormal blood flow. Age-related macular degeneration is technically included under the umbrella term retinopathy but is often discussed as a separate entity. Retinopathy, or retinal vascular disease, can be broadly categorized into proliferative and non-proliferative types. Frequently, retinopathy is an ocular manifestation of systemic disease as seen in diabetes or hypertension. Diabetes is the most common cause of retinopathy in the U.S. as of 2008. Diabetic retinopathy is the leading cause of blindness in working-aged people. It accounts for about 5% of blindness worldwide and is designated a priority eye disease by the World Health Organization.Rod cell
Rod cells are photoreceptor cells in the retina of the eye that can function in less intense light than the other type of visual photoreceptor, cone cells. Rods are usually found concentrated at the outer edges of the retina and are used in peripheral vision. On average, there are approximately 92 million rod cells in the human retina. Rod cells are more sensitive than cone cells and are almost entirely responsible for night vision. However, rods have little role in color vision, which is the main reason why colors are much less apparent in dim light, and not at all at night.Virtual retinal display
A virtual retinal display (VRD), also known as a retinal scan display (RSD) or retinal projector (RP), is a display technology that draws a raster display (like a television) directly onto the retina of the eye. The user sees what appears to be a conventional display floating in space in front of them.Visual prosthesis
A visual prosthesis, often referred to as a bionic eye, is an experimental visual device intended to restore functional vision in those suffering from partial or total blindness. Many devices have been developed, usually modeled on the cochlear implant or bionic ear devices, a type of neural prosthesis in use since the mid-1980s. The idea of using electrical current (e.g., electrically stimulating the retina or the visual cortex) to provide sight dates back to the 18th century, discussed by Benjamin Franklin, Tiberius Cavallo, and Charles LeRoy.