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J. Kaur, S. Bolz, T. van Veen, B. Arango-Gonzalez; Modifications in Retinal Neurons and Synaptic Connectivity During Photoreceptor Degeneration in Two Rat Models for Retinitis Pigmentosa: S334ter-3 and P23H-1 Rhodopsin Mutations. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4070.
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The central aim of this study was to evaluate changes in cone photoreceptors, horizontal cells and synaptic markers during retinal degeneration.
Retinas from heterozygous P23H-1, S334ter-3 and CD rats were collected at various postnatal ages (PN0 - PN30) and were immunostained with cell-type-specific markers.
We found that at PN30 almost all cones survive after the initial degeneration of the rods in both mutant models. During this time, cones fist lose their outer segments and they partially retract (P23H-1) or lose (S334ter-3) their axon and synaptic pedicle. However, they retain their laminar position, continue expressing opsin and show a polarized morphology. At this age, the gap junctions in the pedicles of adjacent cones stained with connexin36 antibody were clearly reduced in P23H-1 and no longer expressed in the S334ter-3 retina.mGluR6 (post-synaptic marker) immunostaining localized to the dendritic tips of ON bipolar cells was reduced in both mutants. A similar decline in the number of photoreceptor terminals immunostained with bassoon (pre-synaptic marker) was also found. No alteration in the IPL staining was observed. Horizontal cells immunostained with calbindin showed normal sized somata but the density of their processes in the OPL was reduced. We found soma displacement into the remaining ONL and we observed sprouting of processes from horizontal cells in P23H-1 and S334ter-3, oriented radially towards the INL. In the case of S334ter, these processes were longer and they end at the border with the IPL.
Our findings show that during the course of photoreceptor degeneration in both transgenic rats, there are progressive degenerative changes that are very similar to those described in other animal models of retinitis pigmentosa. We believe that several alterations in second-order neurons have common mechanisms independent of the primary cause of the photoreceptor degeneration and should be carefully taken into consideration while working towards the development of neuroprotective treatments.
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