1.Overview. When an ophthalmologist uses an ophthalmoscope to look into your eye he sees the following view of the retina (Fig. 1). In the center of the retina is the optic nerve, a circular to oval white area measuring about 2 x 1.5 mm across. From the center of the optic nerve radiates the major blood vessels of the retina. Approximately 17 degrees (4.5-5 mm), or two and half disc diameters to the left of the disc, can be seen the slightly oval-shaped, blood vessel-free reddish spot, the fovea, which is at the center of the area known as the macula by ophthalmologists. Fig. 1. Retina as seen through an opthalmoscope A circular field of approximately 6 mm around the fovea is considered the central retina while beyond this is peripheral retina stretching to the ora serrata, 21 mm from the center of the retina (fovea). The total retina is a circular disc of between 30 and 40 mm in diameter (Polyak, 1941; Van Buren, 1963; Kolb, 1991). Fig. 1.1. A schematic section through the human eye with a schematic enlargement of the retina The retina is approximately 0.5 mm thick and lines the back of the eye. The optic nerve contains the ganglion cell axons running to the brain and, additionally, incoming blood vessels that open into the retina to vascularize the retinal layers and neurons (Fig. 1.1). A radial section of a portion of the retina reveals that the ganglion cells (the output neurons of the retina) lie innermost in the retina closest to the lens and front of the eye, and the photosensors (the rods and cones) lie outermost in the retina against the pigment epithelium and choroid. Light must, therefore, travel through the thickness of the retina before striking and activating the rods and cones (Fig. 1.1). Subsequently the absorbtion of photons by the visual pigment of the photoreceptors is translated into first a biochemical message and then an electrical message that can stimulate all the succeeding neurons of the retina. The retinal message concerning the photic input and some preliminary organization of the visual image into several forms of sensation are transmitted to the brain from the spiking discharge pattern of the ganglion cells. A simplistic wiring diagram of the retina emphasizes only the sensory photoreceptors and the ganglion cells with a few interneurons connecting the two cell types such as seen in Figure 2. Fig. 2. Simple organization of the retina When an anatomist takes a vertical section of the retina and processes it for microscopic examination it becomes obvious that the retina is much more complex and contains many more nerve cell types than the simplistic scheme (above) had indicated. It is immediately obvious that there are many interneurons packed into the central part of the section of retina intervening between the photoreceptors and the ganglion cells (Fig 3). All vertebrate retinas are composed of three layers of nerve cell bodies and two layers of synapses (Fig. 4). The outer nuclear layer contains cell bodies of the rods and cones, the inner nuclear layer contains cell bodies of the bipolar, horizontal and amacrine cells and the ganglion cell layer contains cell bodies of ganglion cells and displaced amacrine cells. Dividing these nerve cell layers are two neuropils where synaptic contacts occur (Fig. 4). The first area of neuropil is the outer plexiform layer (OPL) where connections between rod and cones, and vertically running bipolar cells and horizontally oriented horizontal cells occur (Figs. 5 and 6). Fig. 5. 3-D block of retina with OPL highlighted Fig. 6. Light micrograph of a vertical section through the OPL The second neuropil of the retina, is the inner plexiform layer (IPL), and it functions as a relay station for the vertical-information-carrying nerve cells, the bipolar cells, to connect to ganglion cells (Figs. 7 and 8). In addition, different varieties of horizontally- and vertically-directed amacrine cells, somehow interact in further networks to influence and integrate the ganglion cell signals. It is at the culmination of all this neural processing in the inner plexiform layer that the message concerning the visual image is transmitted to the brain along the optic nerve. Fig. 7. 3-D block of retina with IPL highlighted Fig. 8. Light micrograph of a vertical section through the OPL 2. Central and peripheral retina compared. Central retina close to the fovea is considerably thicker than peripheral retina (compare Figs. 9 and 10). This is due to the increased packing density of photoreceptors, particularly the cones, and their associated bipolar and ganglion cells in central retina compared with peripheral retina. Fig. 9. Light micrograph of a vertical section through human central retina Fig. 10. Light micrograph of a vertical section through human peripheral retina Central retina is cone-dominated retina whereas peripheral retina is rod-dominated. Thus in central retina the cones are closely spaced and the rods fewer in number between the cones (Figs. 9 and 10). The outer nuclear layer (ONL), composed of the cell bodies of the rods and cones is about the same thickness in central and peripheral retina. However in the peripheral the rod cell bodies outnumber the cone cell bodies while the reverse is true for central retina. In central retina, the cones have oblique axons displacing their cell bodies from their synaptic pedicles in the outer plexiform layer (OPL). These oblique axons with accompanying Muller cell processes form a pale-staining fibrous-looking area known as the Henle fibre layer. The latter layer is absent in peripheral retina. The inner nuclear layer (INL) is thicker in the central area of the retina compared with peripheral retina, due to a greater density of cone-connecting second-order neurons (cone bipolar cells) and smaller-field and more closely-spaced horizontal cells and amacrine cells concerned with the cone pathways (Fig. 9). As we shall see later, cone-connected circuits of neurons are less convergent in that fewer cones impinge on second order neurons, than rods do in rod-connected pathways. A remarkable difference between central and peripheral retina can be seen in the relative thicknesses of the inner plexiform layers (IPL), ganglion cell layers (GCL) and nerve fibre layer (NFL) (Figs. 9 and 10). This is again due to the greater numbers and increased packing-density of ganglion cells needed for the cone pathways in the cone-dominant foveal retina as compared the rod-dominant peripheral retina. The greater number of ganglion cells means more synaptic interaction in a thicker IPL and greater numbers of ganglion cell axons coursing to the optic nerve in the nerve fibre layer (Fig. 9). 3. Muller glial cells. Fig. 11. Vertical view of Golgi stained Muller glial cells Muller cells are the radial glial cells of the retina (Fig. 11). The outer limiting membrane (OLM) of the retina is formed from adherens junctions between Muller cells and photoreceptor cell inner segments. The inner limiting membrane (ILM) of the retina is likewise composed of laterally contacting Muller cell end feet and associated basement membrane constituents. The OLM forms a barrier between the subretinal space, into which the inner and outer segments of the photoreceptors project to be in close association with the pigment epithelial layer behind the retina, and the neural retina proper. The ILM is the inner surface of the retina bordering the vitreous humor and thereby forming a diffusion barrier between neural retina and vitreous humor (Fig. 11). Throughout the retina the major blood vessels of the retinal vasculature supply the capillaries that run into the neural tissue. Capillaries are found running through all parts of the retina from the nerve fibre layer to the outer plexiform layer and even occasionally as high as in the outer nuclear layer. Nutrients from the vasculature of the choriocapillaris (cc) behind the pigment epithelium layer supply the delicate photoreceptor layer. 4. Foveal structure. The center of the fovea is known as the foveal pit (Polyak, 1941) and is a highly specialized region of the retina different again from central and peripheral retina we have considered so far. Radial sections of this small circular region of retina measuring less than a quarter of a millimeter (200 microns) across is shown below for human (Fig. 12a) and for monkey (Fig.12b). Fig. 12a. Vertical section of the human fovea from Yamada (1969) Fig. 12b. Vertical section of the monkey fovea from Hageman and Johnson (1991) The fovea lies in the middle of the macula area of the retina to the temporal side of the optic nerve head (Fig. 13a, A, B). It is an area where cone photoreceptors are concentrated at maximum density, with exclusion of the rods, and arranged at their most efficient packing density which is in a hexagonal mosaic. This is more clearly seen in a tangential section through the foveal cone inner segments (Fig. 13b). Fig 13a. A) fundus photo of a normal human macula, optic nerve and blood vessels around the fovea. B) Optical coherence tomography (OCT) images of the same normal macular in the area that is boxed in green above (A). The foveal pit (arrow) and the sloping foveal walls with dispelled inner retina neurons (green and red cells) are clearly seen. Blue cells are the packed photoreceptors, primarily cones, above the foveal center (pit). Fig. 13. Tangential section through the human fovea Below this central 200 micron diameter central foveal pit, the other layers of the retina are displaced concentrically leaving only the thinnest sheet of retina consisting of the cone cells and some of their cell bodies (right and left sides of Figs. 12a and 12b). This is particularly well seen in optical coherence tomography (OCT) images of the living eye and retina (Fig. 13a, B). Radially distorted but complete layering of the retina then appears gradually along the foveal slope until the rim of the fovea is made up of the displaced second- and third-order neurons related to the central cones. Here the ganglion cells are piled into six layers so making this area, called the foveal rim or parafovea (Polyak, 1941), the thickest portion of the entire retina. 5. Macula lutea. The whole foveal area including foveal pit, foveal slope, parafovea and perifovea is considered the macula of the human eye. Familiar to ophthalmologists is a yellow pigmentation to the macular area known as the macula lutea (Fig. 14). This pigmentation is the reflection from yellow screening pigments, the xanthophyll carotenoids zeaxanthin and lutein (Balashov and Bernstein, 1998), present in the cone axons of the Henle fibre layer. The macula lutea is thought to act as a short wavelength filter, additional to that provided by the lens (Rodieck, 1973). As the fovea is the most essential part of the retina for human vision, protective mechanisms for avoiding bright light and especially ultraviolet irradiation damage are essential. For, if the delicate cones of our fovea are destroyed we become blind. Fig. 14. Ophthalmoscopic appearance of the retina to show macula lutea Fig. 15. Vertical section through the monkey fovea to show the distribution of the macula lutea. From Snodderly et al., 1984 The yellow pigment that forms the macula lutea in the fovea can be clearly demonstrated by viewing a section of the fovea in the microscope with blue light (Fig. 15). The dark pattern in the foveal pit extending out to the edge of the foveal slope is caused by the macular pigment distribution (Snodderly et al., 1984). Fig. 16. Appearance of the cone mosaic in the fovea with and without macula lutea If one were to visualize the foveal photoreceptor mosaic as though the visual pigments in the individual cones were not bleached, one would see the picture shown in Figure 16 (lower frame) (picture from Lall and Cone, 1996). The short-wavelength sensitive cones on the foveal slope look pale yellow green, the middle wavelength cones, pink and the long wavelength sensitive cones, purple. If we now add the effect of the yellow screening pigment of the macula lutea we see the appearance of the cone mosaic in Figure 16 (upper frame). The macula lutea helps enhance achromatic resolution of the foveal cones and blocks out harmful UV light irradiation (Fig. 16 from Abner Lall and Richard Cone, unpublished data). 6. Ganglion cell fiber layer. The ganglion cell axons run in the nerve fiber layer above the inner limiting membrane towards the optic nerve head in a arcuate form (Fig. 00, streaming pink fibers). The fovea is, of course, free of a nerve fiber layer as the inner retina and ganglion cells are pushed away to the foveal slope. The central ganglion cell fibers run around the foveal slope and sweep in the direction of the optic nerve. Peripheral ganglion cell axons continue this arcing course to the optic nerve with a dorso/ventral split along the horizontal meridian (Fig. 00). Retinal topography is maintained in the optic nerve, through the lateral geniculate to the visual cortex. Fig. 00. Schematic representation of the course of ganglion cell axons in the retina. The retinotopic origin of these nerve fibers is respected throughout the visual pathway. (Modified from Harrington DO, Drake MV. The visual fields. 6th ed. St. Louis: CV Mosby; 1990, with permission) Source
