Pathological analyses of retinal degeneration in prosaposin transgenic mice

2015 Fiscal Year Final Research Report

• Project/Area Number: 26861476
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Kawasaki Medical School
• Principal Investigator: Ono Koji 川崎医科大学, 医学部, 講師 (00548597)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: プロサポシン / サポシン / 網膜色素変性症 / 視細胞 / 網膜色素上皮細胞 / オートファジー

Outline of Final Research Achievements

Prosaposin (PSAP) is a precursor protein of four saposins, which are required for the intra lysosomal degradation of sphingolipids, and is also secreted into extra-cellular space as a trophic factor. The deficiency of semaphorin 4A (Sema4A), were reported to cause photoreceptor cell degeneration due to the impaired secretion of PSAP from the retinal pigment epithelial cells (RPE). In the present study, we characterized the retinal phenotypes of Psap knock-out (Psap-KO) mice and PSAP transgenic (PSAP-Tg) mice which have strong, stable, and ubiquitous expression of PSAP. In the retinas of Psap-KO mice, no apparent photoreceptor cell degeneration were observed.In contrast, in the retinas of PSAP-Tg mice, almost all the photoreceptor cells were disappeared by 6 weeks of age. These findings indicate that PSAP and SAPs play a critical role in retina, and intra-cellular accumulation of PSAP and SAPs cause retinal photoreceptor cell degeneration.

Free Research Field

脂質生化学