Investigation of a new mechanism of age-related macular degeneration using a rat model of retinal photic injury: targeted exome analysis for a responsible genomic region

2016 Fiscal Year Final Research Report

• Project/Area Number: 25462708
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Ohishi Kentaro 浜松医科大学, 光尖端医学教育研究センター, 助教 (80345826)
• Co-Investigator(Kenkyū-buntansha): 大坪 正史 浜松医科大学, 光尖端医学教育研究センター, 助教 (10327653) ; 尾花 明 浜松医科大学, 光尖端医学教育研究センター, 客員教授 (40194625) ; 堀田 喜裕 浜松医科大学, 医学部, 教授 (90173608) ; 蓑島 伸生 浜松医科大学, 光尖端医学教育研究センター, 教授 (90181966)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 網膜光障害 / ラット / 戻し交配 / 系統差 / 責任遺伝子 / エキソーム解析 / 加齢黄斑変性

Outline of Final Research Achievements

PURPOSE: To identify genes for photic injury susceptibility of rat retina, eventually to elucidate an etiology for age-related macular degeneration (AMD). METHODS: A retinal degeneration size showing the susceptibility was evaluated on pathological specimens. A targeted exome analysis was performed with MiSeq system (illumina, Inc.). RESULTS: We performed the targeted exome analysis for 3.8-Mb Rpi1 region among resistant (LEW) and susceptible (WKY and F344) strains and found 3 loci with non-synonymous base changes in 2 genes. In parallel, obtained BC9 offspring had a 284-kb WKY genome region as a sole WKY component, and in which only 1 locus in 1 gene (tentatively gene R) was narrowed down. CONCLUSION: We consider that the gene R is Rpi1 itself. The gene R has never been reported as the susceptibility gene of AMD. We are now extensively making efforts to give more direct evidence for the gene R as the causal gene of rat retinal photic injury and possible relationship with AMD.

Free Research Field

医歯薬学