Abstract
Abstract: :
Purpose:In animal models of hereditary retinal degeneration, previous results (PNAS 90:8484–8488) have implicated cell–to–cell interactions that may cause rod degeneration in addition to the cell–autonomous mechanisms activated by mutations. We tested the hypothesis that the rod–to–rod bipolar cell synapse may be a site of the proposed cell–to–cell interactions. Methods:We performed immunocytochemical and EM analyses on retinal sections obtained from 5–week–old normal (C57/BL/6J) and rhodopsin (P347S) transgenic mice. Results:In P347S mice, 70% of photoreceptor nuclei remained and outer segment lengths were near normal. Rod b–wave ERG amplitude was 40 % of normal. Ectopic cone–to–rod bipolar cell synapses were identified by EM PKCα–labeling of rod bipolar cell dendrites. Of all the rod synaptic terminals counted, only 49% had a "triad", compared to 86% in C57/BL/6J; 18% had only a "dyad", compared to 11% in C57/BL/6J. Terminals with only a floating synaptic ribbon were observed in 23% of P347S synapses, compared to 3% in C57/BL/6J. Most strikingly, 10% of P347S synapses showed a vacant space opposite to the ribbon, a site normally occupied by rod bipolar cell dendrites, in the synaptic complex where the elements contributed by the horizontal cells ("dyad") also remained. Such "incomplete triads" were not observed in C57/BL/6J. Conclusions:In rod synaptic terminals of degenerating retinas, there was selective loss of invaginating elements contributed by rod bipolar cell dendrites. Our data suggested a scenario that as some rods degenerate autonomously, the rod bipolar cell, which through its many dendrites makes synaptic connections with multiple rods, may withdraw some of its dendrites from existing synaptic complexes in rods and make synapses with other photoreceptors. This action by the rod bipolar cell would accelerate rod degeneration in the retina and may underlie the proposed mechanism of cell–to–cell interactions.
Keywords: retinal degenerations: cell biology • bipolar cells • photoreceptors