Research projects

太陽光に含まれる波長380nmのバイオレットライト(Violet Light: VL)は非視覚光受容体であるOpn5によって受容され、シグナルとして広範囲の組織に影響を及ぼす。近年VLがOpn5を介して網膜血管に対して影響を及ぼすことが報告された。本研究ではVLによる血管新生制御の機構を詳細に検討する。さらに網膜色素上皮における脂質代謝へのVL寄与とその機能の詳細を明らかにし、脈絡膜血管新生に対するVLの影響を示す。以上より、Opn5によって非視覚受容されたVLがいかにして脈絡膜局所の血管形成に対する制御を行うかを明らかにし、VLによる脈絡膜血管新生由来疾患の新規治療法の確立を目指す。

Lipid metabolism-related gene mutations can cause retinitis pigmentosa, a currently untreatable blinding disease resulting from progressive neurodegeneration of the retina. Here, we demonstrated the influence of adiponectin receptor 1 (ADIPOR1) deficiency in lipid metabolism and retinal neurodegeneration using Adipor1 knockout (KO) mice. Photoreceptors of KO mice were misaligned and their lipid composition, including DHA, which is critical in forming photoreceptor outer segments, was impaired in the retina. Importantly, the expression of Elovl2, an elongase of very long chain fatty acids, was significantly reduced, and lipogenic genes, which are induced under conditions of reduced endogenous DHA synthesis, were increased in KO mice. Therefore, ADIPOR1 in the retina appears to be indispensable for ELOVL2 induction, which is likely required in the retinal local lipid metabolism to supply sufficient DHA for appropriate photoreceptor function and survival.

Adiponectin receptor 1 (AdipoR1) is expressed in various organs, including skeletal muscle, the liver, the spleen, and the retina. AdipoR1 is a well-known receptor of adiponectin, a major regulator of glucose and lipid homeostasis. Recent studies have reported that the mutation of AdipoR1 gene causes retinal degeneration, but its detailed mechanism remains unknown. Here we reported the detailed phenotype of retinal degeneration caused by AdipoR1 mutation. The mutation of AdipoR1 showed the retinal degeneration from very early stage of retinal development, and the severe retinal dysfunction. This indicates the important function of AdipoR1 in retinal development.