斑马鱼crb2b基因突变对视网膜光感受器细胞发育的影响

视网膜色素变性（RP）是一种遗传性致盲眼病，光感受器细胞进行性死亡是导致其视力丧失的主要原因，因而对光感受器细胞退变机制的研究非常重要。CRB1基因突变与人类RP相关。斑马鱼视网膜光感受器细胞以视锥细胞为主，在一些视网膜疾病的研究上具有独特优势。研究发现斑马鱼Crb2b功能与人类CRB1功能相同。我们在前期工作中已成功构建了crb2b转基因斑马鱼系。本课题主要通过观察和检测不同年龄crb2b转基因斑马鱼视网膜发育中不同区域光感受器细胞的数目、结构以及顶端、粘附等相关蛋白的表达；并与同年龄野生型斑马鱼比较研究斑马鱼crb2b基因突变对视网膜光感受器细胞发育的影响，为RP提供动物模型，有助于进一步揭示RP发生的分子机制。通过观察Crb2b功能丧失对祖细胞及光感受器细胞增生及凋亡的影响研究Crb2b在斑马鱼视网膜再生中的作用，有望恢复人类光感受器细胞的自我修复能力，从而为RP提供有效的治疗方法。

Retinitis pigmentosa (RP) is a hereditary blindness disease, the leading cause of vision loss is the progressive death of photoreceptor cells, so it is very important to study on the mechanism of retinal photoreceptor degeneration. CRB1 gene mutation is associated with RP in humans. Zebrafish retinal photoreceptor cells consist mainly of cone cells, thus zebrafish has the unique superiority in the study of some retinal diseases. The study found that the function of zebrafish Crb2b is identical to that of human CRB1. We have successfully established a crb2b transgenic zebrafish line in our previous work. We intend to compare the number and structure, as well as expression of apical, adhesive proteins of photoreceptor cells in different retinal regions of different age stages of crb2b transgenic zebrafish with the same age of wildtype zebrafish todiscuss the effects of crb2b gene mutation on zebrafish photoreceptor development. Our animal model will help to further in-depth study the pathogenesis of RP. We also intend to investigate the effects of Crb2b dysfunction on proliferation and death of progenitor and photoreceptor cells to discuss the role of Crb2b in the zebrafish retinal regeneration. Our research finding will be expected to restore the self-repair capacity of photoreceptor cells in humans, in order to provide effective treatment for RP.