NEURO2024
森 日菜子さん
今回、2024年７月２４日から２７日に福岡で行われましたNeuro2024に参加させていただきました。そこで、「P2Y₁ receptor deficiency in Müller cells induces glaucoma-like pathology（ミューラー細胞における P2Y1受容体欠損は正常 眼圧緑内障様の傷害を誘導する）」というタイトルでポスター発表させていただきました。
今回、参加させていただき、ポスター発表させていただいたことで、今後の活動のモチベーションの向上につながりました。またこのような発表の機会をいただけるように研究に励んでいく所存です。
今回、発表に際してご指導、ご協力いただきました、小泉先生、篠崎先生はじめ薬理学講座の皆様、ライフサイエンスコース事務局の皆様にこの場をお借りして感謝申し上げます。
以下が抄録となります。
Glaucoma is a leading cause of blindness worldwide, primarily attributed to damage to the retinal ganglion cells (RGCs) responsible for transmitting visual information to the brain. Despite elevated intraocular pressure (IOP) being a well-known risk factor, a majority of Japanese patients present with normal IOP levels. In this study, we unveil a glaucoma-like pathology without IOP elevation, linked to dysfunction in the purinergic system within Müller cells. We revealed the functional expression of P2Y1 receptors (P2Y1Rs) in Müller cells, a retina-specific astrocyte-lineage cell. Given that global P2Y1R knockout (KO) mice exhibited glaucoma-like pathology with high IOP, we hypothesized that P2Y1R deficiency specifically in Müller cells could be associated with glaucoma development. Müller cell-specific P2Y1KO (cKO) mice, regardless of age (3 or 12 months old), did not show significant IOP elevation. However, at 12 months old (12mo-cKO), these mice exhibited an age-associated reduction in the number of Rbpms-positive RGCs compared to control (Ctr) mice, along with an increase in TUNEL-positive cells, indicating apoptotic cell death in RGCs. Optical coherence tomography revealed thinning of the nerve fiber layer in the cKO retina, indicative of damage to RGCs and their axons. Behavioral analyses using optomotor response (OMR) and visual cliff task (VC) demonstrated reduced responses in 12mo-cKO mice compared to age-matched Ctr mice. Electrophysiological estimation through positive scotopic threshold response (pSTR) of electroretinogram indicated a significantly smaller pSTR amplitude in cKO mice, reflecting reduced visual function. Further insights into the pathogenetic mechanism were gained through retinal gene expression analysis by RNA sequencing. The most up-regulated KEGG pathways were neurodegeneration-related, particularly genes encoding mitochondrial complexes I through IV, suggesting increased mitochondrial function. Elevated mitochondrial activity can lead to reactive oxygen species production, and indeed, the cKO retina exhibited enhanced oxidative stress. In conclusion, our data demonstrate that cKO mice exhibit age-associated normal-tension glaucoma-like pathologies characterized by altered metabolism and increased oxidative stress.
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「ジュニア研究者ポスター賞」を受賞されました。
おめでとうございます！
