Morphological Changes Of Retinal Ganglion Cells In RCS Rat During Retinal Degeneration

Retinitis pigmentosa (RP) is one of the most common etiological factors for hereditary blind by loss photoreceptor cells. Several therapeutic strategies for retina degeneration, such as retinal transplantation, gene therapy, visual prosthesis, drug application, were developed in recent years. However, no effective treatment methods to prevent progressive retinal degeneration or to restore visual function have been established. The exact pathophysiological mechanism of retinal degeneration is not fully elucided, which need further explore.Retinal ganglion cells (RGCs) are the third levels of neurons in the retina and is the first development neurons in retina. The dendrites of RGCs communicated with cone bipolar cells as well as amacrine cells. The axons of RGCs are an important part of optic nerve.Basis on the before research on the chronic ocular hypertension, glaucoma and retinal detachment, the numbers of RGCs dendritic branch progressively decreased in the development of the disease. Numerous studies of retinal degeneration in animal model have found that the number of RGCs decreased significantly in the early stage lesions with the progressive loss of photoreceptor cells, whereas the survival of ganglion cell morphology has not changed. Previous results from our laboratory or others have shown that the number of ganglion cells decreased significantly in the early stage of RCS rats (Royal college of surgeon rat, RCS) retinal degeneration. However, the morphology of the survival of theαsubtypes of RGCs in the process of retinal degeneration is not fully clarifed. Taken together, we hypothesize that: the morphology of cone bipolar cells changed following the death of photoreceptor cells during the RCS ratsretinal degeneration. This morphology change may lead to the abnormal communication with RGCs, resulting in the morphology change of the most sensitiveαisoform of RGCs.Our main results are showed as following:1. The DiI staining method was used to study the morphological changes of the α-RGCs during the pathological process of RCS rat. The results showed that: In the pathological development of the retina of the RCS rats , the amount of first and second level of dendrite branching, the diameter of first level of dendrite branching, and the frequency of dendrite branching ofαsubgroup of retinal ganglion cells were determined. Dendritic branching frequency is the number of dendritic branching, reflecting the changes in the number of dendrites. There was significant difference of frequency of dendrite branching compare with RCS-rdy+ rats. There was also significant difference of the diameter of first level of dendrite branching between RCS and the RCS-rdy+ rats of different ages. But there was no significant difference of the amount of first and second level of dendrite branching between RCS-P+and RCS-rdy+ rats of different ages. Dendrites of RGCs is to receive incoming nerve signals the main parts of dendritic morphogenesis of synaptic signal input, processing and neural circuit formation play an important role. Whether this change in dendritic morphology occur the process of retinal degeneration due to neuronal survival in the microenvironment change need to be further studied.2.The immunohistochemical method was used to study the axon density of cone bipolar cells during the pathological process of RCS rat. Results: Recoverin positive cone bipolar cell axon density began to decrease at P30d, P90d showed significantly reduced following the outer nuclear layer of retinal photoreceptor cells deletion during the RCS rat retinal degeneration process. The results suggest that, after losing on an incoming signal, the morphology of cone bipolar cells changes inevitably. Such reduction in axon density may be the next level of input neurons influence.Our main conclusion is showed as following:In the pathological development of retinitis pigmentosa, frequency of dendrite branching ofαsubgroup of retinal ganglion cells increased significantly in the early stage, while the frequency of dendrite branching decreased during middle and late stage. Our research suggests that the process ofαsubgroup of retinal ganglion cells in the retinal degeneration of dendrites of the information transmission function may have changed.