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E Strettoi, V Pignatelli, C Rossi; Morphological Abnormalities of Second Order Neurons in Animal Models of Retinitis Pigmentosa . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3666.
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Purpose: To study the morphology of inner retinal neurons in animal models of retinitis pigmentosa. The viability of inner retinal cells is of great relevance in view of the possibility to restore vision in retinal degeneration by means of photoreceptor transplant or direct stimulation of the inner cells. Methods: Animals were rd/rd mutant mice of the C3H Pde strain and control C57 Bl mice. Retinal cells were labeled by means of immunocytochemistry for cell-type specific antibodies, gene gun delivery of DiI and DiO, and examined by means of confocal and electron microscopy. Antibodies were: PKC and L7 (for rod bipolars); caldendrin and NK3 (for cone bipolars); calbindin D (for horizontal cells); neurofilaments 200kD (for axonal arborizations of horizontal cells); ChAt (for cholinergic amacrines); TH (for dopaminergic amacrines); disabled 3 (for AII amacrines). In the attempt to prevent dendritic underdevelopment in bipolar cells, overexpression of the anti-apoptotic gene bcl-2 was induced in the inner retina of rd/rd mice by crossing C3H Pde animals with transgenic mice overexpressing bcl-2 under the neuron-specific enolase promoter. Results: Rd/rd mutant mice udergo degeneration of rods in the first weeks of postnatal life. At a slower rate, cones degenerate as well. We found that, rod bipolar cells of rd retinas show underdeveloped dendritic and axonal arborizations with abnormal synaptic contacts in the ipl. Residual dendrites retract upon total rod degeneration. Cone bipolars develop normally but loose dendrites when photoreceptors have died out. Horizontal cells show initial sprouting; later, they become hypertrophic. Axonal arborization are enormous and loose fine ramifications. On the contrary, amacrine cells appear normal, in number and morphology. Since dendritic underdevelopment and atrophy resemble a typical neuronal reaction to trophic factor deprivation, we developed a novel strain of mice, expressing both the rd/rd mutation and overexpression of bcl-2 in the inner retina. Bcl-2 is know to confer cells the ability to resist axotomy, trophic factor deprivation and ischaemia. Double mutant mice exhibits all the morphological abnormalities described in rd/rd mice, including the atrophy of dendritic and axonal arborizations of bipolar cells. Conclusions: Photoreceptor degeneration affects profoundly the development and the adult morphology of bipolar and and horizontal cells while does not seem to influence amacrine cells. Overexpression of the anti-apoptotic gene bcl-2 is unable to promote dendritic regrowth or to avoid dendritic and axonal atrophy in bipolar cells.
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