Analysis of the retina degeneration mechanism in the absence of synaptic protein CAST/ELKS

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09769
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Tokyo University of Science (2021-2022); University of Yamanashi (2020)
• Principal Investigator: Hagiwara Akari 東京理科大学, 理工学部応用生物科学科, 准教授 (70402849)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 網膜変性疾患 / リボンシナプス / プレシナプス / 視細胞 / 水平細胞 / 異所性局在

Outline of Final Research Achievements

In the retina, which senses optical information from the external environment, the ectopic localization of photoreceptor ribbon synapses has been found to be associated with decreased visual function. In this study, we generated mice lacking the presynaptic proteins CAST and ELKS specifically in retinal or horizontal cells. In contrast to the previous analysis using global knockout of CAST, the immunohistochemical analysis revealed no signs of degeneration such as ectopic localization of ribbon synapses, indicating that CAST expression in photoreceptor and horizontal cells alone does not directly cause the retinal degeneration. However, when CAST was depleted after the synapse formation, it led to the degeneration of photoreceptor cells. Therefore, CAST plays an important role in maintaining the integrity of photoreceptor cells and their synapses.

Free Research Field

シナプス伝達を基盤とした脳神経科学

Academic Significance and Societal Importance of the Research Achievements

網膜機能が障害される網膜変性症では、視細胞が変性し夜盲や視野狭窄といった症状がみられ、視細胞の脱落が進行すると失明にいたることもある。若年性の網膜変性症から多岐にわたる原因遺伝子が同定されてきたが、孤発性の多くは特定の遺伝子異常がないため発症や進行の作用機序がわからず、効果的な治療法も確立されていない。本研究は、視覚機能の低下に相関する視細胞リボンシナプスの異所性局在において、プレシナプスタンパク質の作用機序を明らかにすることで、網膜変性疾患の原因解明や治療法開発に貢献するものである。