Introduction to Basic Anatomy and Physiology of Vision Alan D. Letson, MD Professor & William H. Havener Chair in Ophthalmology Department of Ophthalmology Alan.Letson@osumc.edu Primary Objective Describe the organization of the retina and mechanisms involved in photo transduction. Objectives Describe the arterial blood supply to the orbit, retina and anterior optic nerve Describe the blood supply to the visual cortex Describe venous drainage of the eye and orbit. Describe retinal anatomy and histology Describe the visual cycle of 11 –cis-retinal to all-trans retinal and the relationship of the photoreceptor to the retinal pigment epithelium in this cycle Describe the relationship of the visual cycle to photo transduction. Describe photo transduction and the resultant change in photoreceptor cell polarization and effects at the photoreceptor –bipolar cell synapse Describe the relationship of retinal anatomy to production and organization of visual stimuli Note This module contains a number of “demonstration slides”. These are included to enhance your appreciation of the complexity of the retinal neural organization but are not required for testing purposes. These will be indicated in the notes and narration as “elective” slides. Additional Resources utilized for this module Ryan (editor): Retina, vol 1, 5th edition, 2013 Pages 330430 Basic and Clinical Science Course*: Volume 2 Fundamentals and Principles of Ophthalmology Volume 5 Neuro-Ophthalmology Volume 12 Retina and Vitreous * American Academy of Ophthalmology What does the retina do? Blood supply to the visual system A Internal and external carotid artery collateral systems Rod outer segments furrows cleft Insert fig 8-2 spencer IRBP Figure 4-6 Photoreceptor mosaic in the primate retina. At the fovea, the cones are small and tightly packed. With increasing eccentricity, rods appear between the cones until, in the periphery, they are numerically dominant. In this photo the cones are larger than rods. The distance is measured from the foveal center (From Wikler KC, Williams RW, Rakic P. Photoreceptor mosaic: number and distribution of rods and cones in the rhesus monkey retina. J Comp Neurol 1990:297:499-508. Figure 4-6 Photoreceptor mosaic in the primate retina. Farther from the fovea, the numbers of rods increase while cone numbers decrease. Distance is measured from fovea. From Wikler KC, Williams RW, Rakic P. Photoreceptor mosaic: number and distribution of rods and cones in the rhesus monkey retina. J Comp Neurol 1990:297:499-508. Figure 4-10 The mosaic of red, green and blue cones in the human retina. This image, taken from a human subject using adaptive optics, shows the distribution of the three cone classes. Blue cones make up a small fraction, 10%, but make a regular mosaic. Red and green cones have a clumpy, random distribution. In this subject, the red cones outnumber the green cones but this ratio is highly variable, even in subjects who have normal color vision. Image courtesy of Austin Roorda, after Roorda A, Williams DR. The arrangement of the three cone classes in the living human eye. Nature 1999;397:520-522.. Vertical retina: Glutamate - excites Horizontal retina: inhibitory Parallel pathways. A highly filtered image, 13 x 20 pixels containing mostly low spatial frequency information. At first, it may be hard to recognize because it is natural to focus on the pixel edges. However, if you squint to blur the image, the true identity of the picture may suddenly be more obvious. This is a direct demonstration that the visual system carries several (approx. 15) parallel streams of visual information with different spatial properties mediated through different ganglion cell types. Figure 4-19 ON and OFF pathways. The opposite responses of ON and OFF cone bipolar cells are generated by the expression of different glutamate receptors. OFF bipolar cells are depolarized by glutamate, the photoreceptor transmitter, hence the + for a sign conserving synapse. ON bipolar cells are hyperpolarized by glutamate, hence the - for a sign inverting synapse. This unusual receptor is called the mGluR6 receptor. It is selectively activated by the glutamate analog APB and it is responsible for the separation of ON and OFF signals through the visual system. Furthermore, the inner retina is functionally stratified. OFF bipolar cells ramify in sublamina a and ON bipolar cells descend to sublamina b. Both bipolar cell types use glutamate and they make excitatory synapses with amacrine and ganglion cells. Glutamate receptors map the rod/cone mosaic. mGluR6 receptors (red) mark the tips of rod bipolar cells where they enter the rod spherule. A small cluster of ON cone bipolar dendrites are also lightly marked at each cone pedicle. GluR5 receptors (blue) mark OFF bipolar cell basal contacts at each cone pedicle. Thus, this combination of glutamate receptor antibodies conveniently marks the positions of rod and cone terminals. Courtesy of Pan and Massey SC. OFF bipolar cells contact cones. An OFF bipolar cell was filled with Lucifer yellow (green). In wholemount, with the focus at the OPL, fine dendrites extend to contact every cone within the dendritic field. The positions of rod and cone terminals are marked with a combination of glutamate receptor antibodies mGluR6 (red) and GluR5 (blue). Figure 4-15 B-type horizontal cells in the rabbit retina. A, A single B-type horizontal cell filled with Lucifer yellow contacts all the cone pedicles (white outlines) within its dendritic field. Arrow shows the axon leaving the frame. A, courtesy of Li W and Massey SC; A series of biotinylated tracers distinguishes three types of gap junction in retina. J Neurosci 2000;20: 8629-8636. With permission from the authors and the society for Neuroscience. B, The rod/cone mosaic is shown by labeling postsynaptic glutamate receptors, GluR5 (blue) and mGluR6 (red). The A-type horizontal cells contact every cone in the frame. Figure 4-14 A-type horizontal cells in the rabbit retina. A, The coupled matrix of A-type horizontal cells following the intracellular injection of Neurobiotin (green) in the rabbit retina. B, The rod/cone mosaic is shown by labeling postsynaptic glutamate receptors, GluR5 (blue) and mGluR6 (red). The A-type horizontal cells contact every cone in the frame. C, At high resolution, fine horizontal cell dendrites (green) converge at individual cone pedicles. D, In the triple label image, the horizontal cells terminate at cone pedicles. The green, red and blue labels are not colocalized. They label independent neuronal structures: horizontal cells, ON bipolar cells and OFF bipolar cells, respectively. Courtesy of Pan and Massey SC. Figure 4-33 Amacrine cell morphology. This figure shows the comparative morphology of 24 distinct amacrine cell types from the rabbit retina. Courtesy of Masland D. Neuronal diversity in the retina. Curr Opin Neurobiol 2001; 11:431-436. With permission from the author and Elsevier. Figure 4-36 S1/S2 matrix. A, The S1/S2 matrix (green), stained by serotonin uptake, from wholemount rabbit retina. B, Rod bipolar terminals (blue) fill holes in the S1/S2 matrix. Figure 4-36 S1/S2 matrix. A, The S1/S2 matrix (green), stained by serotonin uptake, from wholemount rabbit retina. B, Rod bipolar terminals (blue) fill holes in the S1/S2 matrix. C, AII dendrites (red) also contact the same rod bipolar terminals. D, Merged triple label image shows S1/S2 processes and AII dendrites surrounding every rod bipolar terminal. From Zhang J, Li W, Trexler EB and Massey SC. Confocal analysis of reciprocal feedback at rod bipolar terminals in the rabbit retina. J Neurosci 2002; 22:10871-10882. With permission of the authors and the Society for Neuroscience. Figure 9-34 The midget system of the primate retina. The red and green cones each activate two bipolars (ON and OFF) that subserve ON and OFF ganglion cells. The blue system is different: blue cones connect with ON-bipolars, but not OFF-bipolars, and the blue cone bipolars are represented by a special class of bistratified bipolar cell. These cells feed into the parvocellular layer of the lateral geniculate. (From Schiller PH. Prog Retin Eye Res 1995; 15:173-196.) Figure 9-35 The parasol, or M ganglion, cell system is one in which a single, large field ganglion cell receives input from all three cone types, producing a cell that is less interested in color and more interested in luminosity or brightness discrimination. These cells feed into the magnocellular layer of the lateral geniculate. (From Schiller PH. Prog Retin Eye Res 1995; 15:173-196.) Summary items to know: The blood supply of the inner retina and superficial optic disc is derived from the central retinal artery. The outer retina (photoreceptor layers), optic disc and choroid receive blood from the short posterior ciliary arteries, All these are branches of the ophthalmic artery – the first intracranial branch of the internal carotid Summary items to know Our external world is organized point by point, spatially, through sequential synapses from the retina through the visual cortex, each particular portion having a different blood supply. Summary items to know The vitamin A visual cycle between the retinal pigment epithelium and the photoreceptor recycles and provides the material sources (Rhodopsin,11-cis retinal and all-trans retinal) that are required to initiate photo transduction. The specific biochemical steps do not need memorizing, but the general process should be understood. Summary items to know Photo transduction converts light energy into a neural impulse. While the specific biochemical steps do not need memorized, a general description of what happens when light is absorbed by Rhodopsin, the changes that occur when the cation gate is closed and the subsequent hyper polarization of the cell with its subsequent effect on glutamate release at the synapse should be understood. Summary items to know The electrical and subsequent neurotransmitter changes that are initiated by photo transduction are transmitted “vertically” through the retina by photoreceptors, bipolar cells and retinal ganglion cells. The axons of the retinal ganglion cells synapse in the LGN or pretectal nuclei. Summary items to know: This vertical transmission of neural impulse is heavily modulated by “horizontally” inhibitory actions by horizontal cells and amacrine cells, and the receptive fields with onoff zones. This modulation results in the final output from the ganglion cells. This output is in the form of graded responses of various types of simultaneously streaming visual channels of information that provide the components of our vision ( color, contrast, contour, etc). Thank you for completing this module Questions? Contact me at: Alan.Letson@osumc.edu Survey We would appreciate your feedback on this module. Click on the button below to complete a brief survey. Your responses and comments will be shared with the module’s author, the LSI EdTech team, and LSI curriculum leaders. We will use your feedback to improve future versions of the module. 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