Photoreceptor protection by 9-cis-retinoid in retinal degeneration in RPE65-/- mice

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K16954
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Hirosaki University
• Principal Investigator: Maeda-Monai Natsuki 弘前大学, 医学研究科, 客員研究員 (20748769)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 網膜色素変性 / RPE65 / 9-シス－レチナール / 視サイクル

Outline of Final Research Achievements

Mutations in the RPE65 gene have been known to cause retinitis pigmentosa. To confirm the photoreceptor protective effects of 9-cis-retinal, we fed RPE65 knock-out mice by per os administration of 9-cis-retinal on postnatal 27 days old and checked whether we could find photoreceptor protective effects after administration of 9-cis-retinal using optical coherence tomography (OCT) and electroretinography (ERG). Results showed that although there was no morphological difference by OCT, there were statistically significant differences in the amplitudes of ERG a- and b-waves after 7 days of administration of 9-cis-retinal. The result indicated that administration of 9-cis-retinal has a therapeutic potential for retinitis pigmentosa caused by the mutations in the RPE65 gene.

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

RPE65 (retinal pigment epithelium 65kDa protein) は網膜色素上皮において視細胞から運搬された全－トランス－レチナールを11－シス－レチナールに変換することにより11－シス－レチナールの再生を司っている。RPE65遺伝子変異により、11－シス－レチナールの再生が障害されることで視細胞が変性するが、この遺伝子型をもつ網膜色素変性に対しては9－シス－レチナールを経口投与にて摂取することで視細胞変性を抑制することができる可能性があると考えられた。