| Retinitis Pigmentosa (RP) is a group of hereditary retinal degeneration characterized by progressive dysfunction of photoreceptors cells (PRC) and associated with progressive cells loss and eventually atrophy of several retinal layers. It is the common reason of hereditary visual impairment and blindness in clinic. So far, we have made progress on the clinical and basic research in recent years, But the various pathological changes of retinal neurons in the course of RP are not clear.Horizontal cell and bipolar cell are the second-order neurons in retinal, they form triad synapses and normal synapses with photoreceptor. They play a key role in visual information processing and transmission. With the gradual reduction of photoreceptors, As the downstream neurons, they begin to lose the upper information input, how they influenced the normal visual information processing and transmission?We would like to know whether the morphology of rod bipolar cell and horizontal cell change when the retinal degeneration occurs. scholars have studied many models on retinal degeneration,such as P23H rat, retinal detachmented mice, rd, rd1, rd10, FVB/N, crx-/- mice, they found that dendrites of rod bipolar cells and horizontal cells shrinked in the medium-term degeneration, they sprouted new processes and formed ectopic synapses late in the degeneration, there were synaptic markers surround around the ectopic synapses. Because there are big difference on pathogenesis betwen previous animal models and human RP, so the guidance of treatment to restore retinal function is limited. There are many similarities in the etiology and progression between the RCS rat and human, RCS rat has been recognized as a classic model of retinitis pigmentosa. Pathological changes of neurons of the RCS rat will provide clues on protection, rescue and rehabilitation of visual function.In recent years, retinal transplantation, visual prosthesis and retinal prosthetic implantation are the main strategies to restore the retinal. We believe that the key to the success of these strategies including: (1)The second-order neurons of receptors hould maintain a stable morphological structure; (2) Donor tissue or cells can form functional synaptic connections with receptors; (3)Choose appropriate therapeutic time window. Results of this study will provide experimental evidence, theoretical basis and new ideas to the selection of RP genes and molecular therapeutic time window, the stability of implanted cells and prosthesis and the integration of therapeutic precursor cells.Based on the research situation, we adopted retinal frozen sections, immunofluorescence staining and DiI trace labeling to study the morphology changes of horizontal cell and related neurons during retinal degeneration. The study included two parts:Part One: Morphology changes of horizontal cells in RCS rat during retinal degenerationPhotoreceptors and the number of ribbon synapses constantly reduced during the process of retinal degeneration in RCS rat, This process can continue until P90d, photoreceptor and ribbon synapse lost slowly. The thickness of ONL in RCS rats was only 15% of control rats at P2M, and at P3M ONL remained only one layer cells. With the progress of retinal degeneration, at P1M, P45d the axon terminals of horizontal cells had no significant changes. At P3M it changed much and extended to ONL. The results from DiI trace labeling showed that the morphology of dendrites and axon terminals of horizontal cells had no changes at P1M, P45d. However, at P2M they changed significantly: Compared with the normal control group,the field of dendrites and axon terminals became small (P<0.05), the small branches of dendrites and axon terminals lost, and the ratio of dendrite length to axon length also shrinked (P<0.05).Part Two: Morphology changes of rod bipolar cells and amacrine cells in RCS rat during retinal degeneration.The results showed the top dendrites of rod-bipolar cell atrophy at P2M; At P3M the dendrites sprouted new process in RCS rat. there were no changes of amacrine cells'dendrites lamination in INL till the late stage of retinal degeneration.Conclusions:1. The morphology changes of horizontal cell and rod bipolar cell in RCS rats are secondary reactions caused by photoreceptor apoptosis, the stabilization of structure is dependent on photoreceptors.2. The morphology changes of horizontal cell and rod bipolar cell in RCS rats did not affect the lamination of amacrine cells'dendrites in IPL. |
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