User:Alan Horsager/Notebook/Retinal Degeneration

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General Overview of Retinal Degeneration
Photoreceptor cell death is accompanied by changes in the neural retina (Banin et al., 1999; Peng et al., 2000; Strettoi and Pignatelli, 2000; Aleman et al., 2001; Strettoi et al., 2002; Strettoi et al., 2003). The local functional implications are not well understood but could compromise spatial processing and transform the retina into a self-signaling neural assembly(Marc and Jones, 2003), making it difficult to use microelectronic retinal prostheses as a rescue strategy. Genetic rescue techniques have there challenges but have windows of opportunity during the degenerative process (Marc and Jones, 2003).

Robert Marc's Phases of Retinal Degeneration

 * 1) Stage1 Phase I – Rod degeneration; rod photoreceptor outer segments shorten, moving rods through stressed and apoptotic stages. Cone outer segments are truncated as well. Rod neurites sprout and enter the inner retina, extending to the ganglion cell layer.
 * 2) Stage2 Phase II – Cone degeneration; rhodopsin levels rise in rods and rods die at a faster rate. Cone gene expression levels change. The subretinal space collapses with fibrosis by Muller cells (glial seal). Every bipolar and horizontal cell appears to be remodeled. Though some bipolar cells die at this stage, quantitatively, it’s a relatively small fraction of the whole.
 * 3) Stage3 Early Phase III – Progressive neurite remodeling; Complete loss of sensory retina and glial seal becomes more compacted. This seal becomes bound to the neural retina and cannot be removed. Neurons of the INL begin to remodel. Global cell death becomes statistically significant.
 * 4) Stage4 Middle Phase III - Global remodeling; microneuromas (small tumors of abnormal growth) begin to form that include synaptic input from all types of cells. Concurrent and nonbiased neuronal death, cell migration, and rewiring. Rate of death is variable and may depend on the rate of cone cell death. Migration includes bipolar and amacrine cells moving into ganglion cell layer. Movement of amacrine and ganglion cells to the glial seal. Bundles of mixed neurites of all cell types course through the retina. All neurons contain their basic molecular signatures at this point.
 * 5) Stage5 Late Phase III – Plateau remodeling; Cell death persists, including substantial cell death in the INL and ganglion cell layer. IPL becomes thinner. Optic fiber thins. RPE alterations are evident.