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色素上皮衍生因子可延缓遗传性视网膜变性小鼠模型中光感受器的死亡。

Pigment epithelium-derived factor delays the death of photoreceptors in mouse models of inherited retinal degenerations.

作者信息

Cayouette M, Smith S B, Becerra S P, Gravel C

机构信息

Faculté de Médecine, Centre de Recherche Université Laval Robert-Giffard, 2601, de la Canardière, Beauport, Québec, G1J 2G3, Canada.

出版信息

Neurobiol Dis. 1999 Dec;6(6):523-32. doi: 10.1006/nbdi.1999.0263.

Abstract

Pigment epithelium-derived factor (PEDF) is a member of the serine protease inhibitor superfamily produced by retinal pigment epithelial cells in the developing and adult retina. In vitro, it induces neuronal differentiation of retinoblastoma cells and promotes survival of cerebellar granule neurons. The pedf gene is closely linked to an autosomal-dominant locus for retinitis pigmentosa, suggesting that PEDF could be a survival factor for photoreceptors. We have investigated this possibility by injecting PEDF into the eyes of homozygous retinal degeneration (rd) and retinal degeneration slow (rds) mice, two mutants displaying apoptotic photoreceptor loss. This procedure resulted in a transient delay of photoreceptor loss in the rd mouse and a reduction in apoptotic photoreceptor profiles in the rds mouse. We conclude that PEDF can act as a survival-promoting factor for photoreceptors in vivo and could potentially be useful for the treatment of photoreceptor diseases.

摘要

色素上皮衍生因子(PEDF)是丝氨酸蛋白酶抑制剂超家族的成员,由发育中和成年视网膜中的视网膜色素上皮细胞产生。在体外,它可诱导视网膜母细胞瘤细胞的神经元分化,并促进小脑颗粒神经元的存活。PEDF基因与常染色体显性色素性视网膜炎位点紧密相连,这表明PEDF可能是光感受器的存活因子。我们通过将PEDF注射到纯合视网膜变性(rd)和视网膜变性缓慢(rds)小鼠的眼睛中研究了这种可能性,这两种突变体均表现出凋亡性光感受器丧失。此操作导致rd小鼠光感受器丧失出现短暂延迟,rds小鼠中凋亡性光感受器轮廓减少。我们得出结论,PEDF在体内可作为光感受器的促存活因子,并且可能对光感受器疾病的治疗有用。

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