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.

Function

There are about 0.7 to 1.5 million retinal ganglion cells in the human retina. With about 4.6 million cone cells and 92 million rod cells, or 96.6 million photoreceptors per retina, on average each retinal ganglion cell receives inputs from about 100 rods and cones. However, these numbers vary greatly among individuals and as a function of retinal location. In the fovea (center of the retina), a single ganglion cell will communicate with as few as five photoreceptors. In the extreme periphery (edge of the retina), a single ganglion cell will receive information from many thousands of photoreceptors.

Retinal ganglion cells spontaneously fire action potentials at a base rate while at rest. Excitation of retinal ganglion cells results in an increased firing rate while inhibition results in a depressed rate of firing.

thumb|right|300px|A false-color image of a flat-mounted rat retina viewed through a fluorescence microscope at 50x magnification. The optic nerve was injected with a fluorophore, causing retinal ganglion cells to fluoresce.

Types

There is wide variability in ganglion cell types across species. In primates, including humans, there are generally three classes of RGCs:

  • W-ganglion: small, 40% of total, broad fields in retina, excitation from rods. Detection of direction movement anywhere in the field.
  • X-ganglion: medium diameter, 55% of total, small field, color vision. Sustained response.
  • Y-ganglion: largest, 5%, very broad dendritic field, respond to rapid eye movement or rapid change in light intensity. Transient response.

The W, X and Y retinal ganglion types arose from studies of the cat. These physiological types are closely related to the respective morphological retinal ganglion types <math>\gamma</math>, <math>\beta</math> and <math>\alpha</math>.

P-type

P-type retinal ganglion cells project to the parvocellular layers of the lateral geniculate nucleus. These cells are known as midget retinal ganglion cells, based on the small sizes of their dendritic trees and cell bodies. About 80% of all retinal ganglion cells are midget cells in the parvocellular pathway. They receive inputs from relatively few rods and cones. They have slow conduction velocity, and respond to changes in color but respond only weakly to changes in contrast unless the change is great. They have simple center-surround receptive fields, where the center may be either ON or OFF while the surround is the opposite.

thumb|Simulated array of parvocellular +M-L (green on) responses (right) to a natural video (left). Notice the relatively high spatial acuity, and sustained temporal responses in this pathway.

M-type

M-type retinal ganglion cells project to the magnocellular layers of the lateral geniculate nucleus. These cells are known as parasol retinal ganglion cells, based on the large sizes of their dendritic trees and cell bodies. About 10% of all retinal ganglion cells are parasol cells, and these cells are part of the magnocellular pathway. They receive inputs from relatively many rods and cones. They have fast conduction velocity, and can respond to low-contrast stimuli, but are not very sensitive to changes in color. They have much larger receptive fields which are nonetheless also center-surround.

[[File:Natural scenes through the magnocellular "OFF" retinal pathway.ogg|thumb|Simulated array of magnocellular OFF responses (right) to a natural video (left). Notice more transient temporal responses in this pathway, compared to the P-type. This retinal pathway is largely color blind.

Pathology

Degeneration of axons of the retinal ganglion cells (the optic nerve) is a hallmark of glaucoma.

Developmental biology

Retinal growth: the beginning

Retinal ganglion cells (RGCs) are born between embryonic day 11 and post-natal day zero in the mouse and between week 5 and week 18 in utero in human development. In mammals, RGCs are typically added at the beginning in the dorsal central aspect of the optic cup, or eye primordium. Then RC growth sweeps out ventrally and peripherally from there in a wave-like pattern. This process depends on a host of factors, ranging from signaling factors like FGF3 and FGF8 to proper inhibition of the Notch signaling pathway. Most importantly, the bHLH (basic helix-loop-helix)-domain containing transcription factor Atoh7 and its downstream effectors, such as Brn3b and Isl-1, work to promote RGC survival and differentiation.

Growth within the retinal ganglion cell (optic fiber) layer

Early progenitor RGCs will typically extend processes connecting to the inner and outer limiting membranes of the retina with the outer layer adjacent to the retinal pigment epithelium and inner adjacent to the future vitreous humor. The cell soma will pull towards the pigment epithelium, undergo a terminal cell division and differentiation, and then migrate backwards towards the inner limiting membrane in a process called somal translocation. The kinetics of RGC somal translocation and underlying mechanisms are best understood in the zebrafish. The RGC will then extend an axon in the retinal ganglion cell layer, which is directed by laminin contact. The retraction of the apical process of the RGC is likely mediated by Slit–Robo signaling.

Axons from the RGCs will grow and extend towards the optic disc, where they exit the eye. Once differentiated, they are bordered by an inhibitory peripheral region and a central attractive region, thus promoting extension of the axon towards the optic disc. CSPGs exist along the retinal neuroepithelium (surface over which the RGCs lie) in a peripheral high–central low gradient.

Growth into and through the optic nerve

RGCs exit the retinal ganglion cell layer through the optic disc, which requires a 45° turn. This is mediated through a cAMP-dependent mechanism. Additionally, CSPGs and Eph–ephrin signaling may also be involved.

RGCs will grow along glial cell end feet in the optic nerve. These glia will secrete repulsive semaphorin 5a and Slit in a surround fashion, covering the optic nerve which ensures that they remain in the optic nerve. Vax1, a transcription factor, is expressed by the ventral diencephalon and glial cells in the region where the chiasm is formed, and it may also be secreted to control chiasm formation.

Growth at the optic chiasm

When RGCs approach the optic chiasm, the point at which the two optic nerves meet, at the ventral diencephalon around embryonic days 10–11 in the mouse, they have to make the decision to cross to the contralateral optic tract or remain in the ipsilateral optic tract. In the mouse, about 5% of RGCs, mostly those coming from the ventral-temporal crescent (VTc) region of the retina, will remain ipsilateral, while the remaining 95% of RGCs will cross. They will establish the posterior aspect of the optic chiasm border. Additionally, Slit signaling is important here: Heparin sulfate proteoglycans, proteins in the ECM, will anchor the Slit morphogen at specific points in the posterior chiasm border. RGCs will begin to express Robo, the receptor for Slit, at this point, thus facilitating the repulsion.

Contralateral projecting RGCs

RGC axons traveling to the contralateral optic tract need to cross. Shh, expressed along the midline in the ventral diencephalon, provides a repulsive cue to prevent RGCs from crossing the midline ectopically. However, a hole is generated in this gradient, thus allowing RGCs to cross.

Molecules mediating attraction include NrCAM, which is expressed by growing RGCs and the midline glia and acts along with Sema6D, mediated via the plexin-A1 receptor. cAMP seems to be very important in regulating the production of NRP1 protein, thus regulating the growth cones response to the VEGF-A gradient in the chiasm.

Ipsilateral projecting RGCs

The only component in mice projecting ipsilaterally are RGCs from the ventral-temporal crescent in the retina, and only because they express the Zic2 transcription factor. Zic2 will promote the expression of the tyrosine kinase receptor EphB1, which, through forward signaling (see review by Xu et al.) will bind to ligand ephrin B2 expressed by midline glia and be repelled to turn away from the chiasm. Some VTc RGCs will project contralaterally because they express the transcription factor Islet-2, which is a negative regulator of Zic2 production.

Shh plays a key role in keeping RGC axons ipsilateral as well. Shh is expressed by the contralaterally projecting RGCs and midline glial cells. Boc, or Brother of CDO (CAM-related/downregulated by oncogenes), a co-receptor for Shh that influences Shh signaling through Ptch1, seems to mediate this repulsion, as it is only on growth cones coming from the ipsilaterally projecting RGCs. The Nogo receptor is only expressed by VTc RGCs.

Growth in the optic tract

Once out of the optic chiasm, RGCs will extend dorsocaudally along the ventral diencephalic surface making the optic tract, which will guide them to the superior colliculus and lateral geniculate nucleus in the mammals, or the tectum in lower vertebrates.

Myelination

In most mammals, the axons of retinal ganglion cells are not myelinated where they pass through the retina. However, the parts of axons that are beyond the retina, are myelinated. This myelination pattern is functionally explained by the relatively high opacity of myelin—myelinated axons passing over the retina would absorb some of the light before it reaches the photoreceptor layer, reducing the quality of vision. There are human eye diseases where this does, in fact, happen. In some vertebrates, such as the chicken, the ganglion cell axons are myelinated inside the retina.

See also

  • Ganglion cell
  • Receptive field

References

  • Diagram at mit.edu
  • Overview and diagrams at webexhibits.org
  • Neuronbank Wiki page on RGCs
  • NIF Search - Retinal Ganglion Cell via the Neuroscience Information Framework