九州大学-研究者情報 [納富昭司 (助教) 九州大学病院眼科]

Shoji Notomi, Kenji Ishihara, Nikolaos E. Efstathiou, Jong-Jer Lee, Toshio Hisatomi, Takashi Tachibana, Eleni K. Konstantinou, Takashi Ueta, Yusuke Murakami, Daniel E. Maidana, Yasuhiro Ikeda, Shinji Kume, Hiroto Terasaki, Shozo Sonoda, Judith Blanz, Lucy Young, Taiji Sakamoto, Koh-Hei Sonoda, Paul Saftig, Tatsuro Ishibashi, Joan W. Miller, Guido Kroemer, and Demetrios G. Vavvas, Genetic LAMP2 deficiency accelerates the age-associated formation of basal laminar deposits in the retina., Proc Natl Acad Sci U S A. 2019; 116(47):23724-23734., 2019.12, The early stages of age-related macular degeneration (AMD) are characterized by the accumulation of basal laminar deposits (BLamDs). The mechanism for BLamDs accumulating between the retinal pigment epithelium (RPE) and its basal lamina remains elusive. Here we examined the role in AMD of lysosome-associated membrane protein-2 (LAMP2), a glycoprotein that plays a critical role in lysosomal biogenesis and maturation of autophagosomes/phagosomes. LAMP2 was preferentially expressed by RPE cells, and its expression declined with age. Deletion of the Lamp2 gene in mice resulted in age-dependent autofluorescence abnormalities of the fundus, thickening of Bruch's membrane, and the formation of BLamDs, resembling histopathological changes occurring in AMD. Moreover, LAMP2-deficient mice developed molecular signatures similar to those found in human AMD-namely, the accumulation of APOE, APOA1, clusterin, and vitronectin-adjacent to BLamDs. In contrast, collagen 4, laminin, and fibronectin, which are extracellular matrix proteins constituting RPE basal lamina and Bruch's membrane were reduced in Lamp2 knockout (KO) mice. Mechanistically, retarded phagocytic degradation of photoreceptor outer segments compromised lysosomal degradation and increased exocytosis in LAMP2-deficient RPE cells. The accumulation of BLamDs observed in LAMP2-deficient mice was eventually followed by loss of the RPE and photoreceptors. Finally, we observed loss of LAMP2 expression along with ultramicroscopic features of abnormal phagocytosis and exocytosis in eyes from AMD patients but not from control individuals. Taken together, these results indicate an important role for LAMP2 in RPE function in health and disease, suggesting that LAMP2 reduction may contribute to the formation of BLamDs in AMD..

主要総説, 論評, 解説, 書評, 報告書等

全てを見る→

主要学会発表等

全てを見る→

学会活動

所属学会名

日本眼循環学会

日本網膜硝子体学会

日本眼科学会

研究資金

科学研究費補助金の採択状況(文部科学省、日本学術振興会)

2021年度～2023年度, 基盤研究(C), 加齢黄斑変性初期病態モデルにおける網羅的脂質代謝解析.

九大関連コンテンツ

pure2017年10月2日から、「九州大学研究者情報」を補完するデータベースとして、Elsevier社の「Pure」による研究業績の公開を開始しました。

QIR　九州大学学術情報リポジトリシステム情報科学研究院

九州大学病院


	※ 研究者情報全体を検索する場合は右端の「すべて」を選択して下さい。