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Corinne Beier, Jennifer Kung, Seungjun Lee, Philip Huie, Roopa Dalal, Daniel V Palanker, Alexander Sher; Bipolar Cells Restructure Dendrites to Make Synaptic Contacts with Healthy Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1476.
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© ARVO (1962-2015); The Authors (2016-present)
In the rabbit retina there is evidence of constructive retinal plasticity in response to focal ablation of a small patch of the photoreceptor layer by laser photocoagulation. Over a few months, healthy photoreceptors migrate inwards filling the damaged area and restoring visual sensitivity to the bipolar cells within the lesion site at 4 months. We investigated the changes in the morphology of the rod bipolar cells (RBCs) beneath the lesion during the healing process to understand how deafferented bipolar cells make new synaptic contacts with healthy photoreceptors.
Line-shaped lesions of Barely Visible clinical grade were produced in rabbits with a 532-nm laser, using beam diameter 100 μm, scanned at 1.0m/s and 1.7m/s along 1.5mm of inferior retina. Retinal ganglion cell responses to spatio-temporal white noise stimulus were recorded on a 512-electrode array. Functional healing was characterized as a return of visual sensitivity over the lesion site, assessed at scotopic and photopic light levels. Photoreceptor migration and changes in RBCs were visually assessed using immunohistochemistry with confocal microscopy. Synaptic contacts between rods and RBCs were visualized with PKCα, ribeye and mGluR6 antibodies.
The lesioned areas of the retina, after a 2 month healing period, regain almost complete visual sensitivity. Immunostaining shows no damage to the inner nuclear layer at 2 days after the procedure with RBCs showing overall normal dendritic structure. Within 1 month the deafferented RBCs restructure their dendrites. Thinner dendrites are pruned and in many cells are replaced by a single thick process reaching perpendicularly out of the lesion. The process extends within the OPL to the lesion border where healthy photoreceptors are and terminates in multiple mGluR6 doublets, coupled with ribbon structures. RBCs extend these processes at varying lengths from their cell bodies, up to twice their reported reach in healthy retina.
The deafferented RBCs are actively seeking viable pre-synaptic partners after the lesioning procedure. The thick processes make synaptic contacts with functional photoreceptors. The resulting dendritic morphology, while not resembling a normal dendritic field, allow RBCs to contact rods in the OPL, unlike ectopic contacts forming in degenerating retinas.
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