Establishment of novel chemical screening assay for risk factors in cone photoreceptors of macular dystrophies

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23707
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0605:Veterinary medical science, animal science, and related fields
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: Otsu Wataru 岐阜薬科大学, 薬学部, 特任助教 (50843091)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: ライソゾーム / 視細胞 / 光障害 / 錐体細胞 / 黄斑ディストロフィー

Outline of Final Research Achievements

It has been known that excessive light stress causes photoreceptor death. Blue light has the shortest wave length of visual light, and therefore is though as a risk for damaging retina and vision loss because of the highest amount of energy. However, it remains less known the molecular mechanism how blue light damages photoreceptors. To address this question, the role of lysosomes in the stress response to blue light was examined. Blue light-emitting diode (LED) light induced lysosomal membrane permeabilization and Transcription Factor EB (TFEB) nuclear transport, resulting in the activation of the lysosome related genes. Antioxidant ameliorate this change, suggesting that oxidative stress is a cause for lysosomal damages. These finding indicates that chemicals which protects lysosomes from light might be a new target for preserving vision from retinal diseases such as macular dystrophy.

Free Research Field

網膜基礎研究

Academic Significance and Societal Importance of the Research Achievements

本研究では、黄斑ディストロフィーの病態解明を目的に実験を行い、光障害に対する視細胞のストレス応答反応におけるライソゾームの重要性について明らかにした。ライソゾームは細胞が取り込んだ物質の消化に関わるのみならず、mTOR経路などを介して、細胞の代謝全体に重要な細胞内小器官である。また、ライソゾームの異常は特に神経変性疾患との関わりがよく知られており、本研究で明らかになった知見は、眼科領域だけでなく、脳や神経の分野において広く貢献できると考えられる。黄斑ディストロフィーは現時点では根治療法がないため、研究成果を更に発展させることにより新たな治療法開発への応用が期待される。