动物造模,药效评价 z-bio 2024-09-03 612

　　The Royal College of Surgeons rat is an autosomal recessive genetic animal model. RCS rat retinal pigment epithelium (RPE) cells express a gene that cannot engulf detached membrane discs, resulting in the loss of photoreceptor cells after birth. At present, it has been found that the recessive gene mutation of RCS rats exists in the Mertek gene of the receptor tyrosinase, which is mainly expressed in the retinal RPE. The deletion mutation of this gene leads to premature termination of the signal at codon 20 after frame shift and open reading frame (ORH) start, which prevents RPE cells from engulfing detached membrane discs. The mutation also exists in human retinitis pigmentosa (RP).

　　【 Model Features 】 Histological observation of RCS rat retina shows an abnormal accumulation layer of external debris between the photoreceptor cell outer segment and the retinal pigment epithelium layer. Normal appearance occurs 2 weeks after birth, and degeneration of the outer nuclear layer cells of the retina begins 20-30 days after birth; At 8 weeks, RPE cells in the posterior pole began to lose; At 10 weeks, in the area where RPE is lost, the endothelial cells of capillaries become thicker and the endothelial window disappears; This process of degeneration and apoptosis continues until 3 months after birth. RCS mutations in rats lead to progressive apoptosis of rod cells, followed by cone cells. Some retinal pigment epithelial cells adjacent to degenerative photoreceptors are taller than normal RPE cells of the same age, with significantly more folds on the basal surface and increased mitochondria in the cytoplasm. At 8 weeks, RPE cells in the posterior pole began to lose; At 10 weeks, in the area where RPE is lost, the endothelial cells of capillaries become thicker and the endothelial window disappears. This degenerative change occurs in different centers of the retina.

　　The Jackson Laboratory and Kyoto University in the United States can provide RCS rat models.

　　RCS rats are the first animal model used for the study of the etiology and treatment of retinal degeneration, and are a mature animal model with many similarities to human retinal degeneration. This model is widely used in the study of retinal degeneration and experimental therapeutic research aimed at slowing down the process of photoreceptor cell loss.