Role of LAMP2 in early pathogenesis of AMD: development of a new animal model

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18880
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Kyushu University
• Principal Investigator: Notomi Shoji 九州大学, 大学病院, 助教 (10836563)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: オートファジー / リソソーム膜タンパク / 加齢性神経変性

Outline of Final Research Achievements

Extracellular tissue debris accumulates with aging and in the most prevalent central-vision-threatening eye disorder, age- related macular degeneration (AMD). In this work, we discovered that lysosome-associated membrane protein-2 (LAMP2), a glycoprotein that plays a critical role in lysosomal biogenesis and maturation of autophagosomes/phagosomes, is preferentially expressed in the outermost, neuroepithelial layer of the retina, the retinal pigment epithelium (RPE), and contributes to the prevention of ultrastructural changes in extracellular basolaminar deposits including lipids and apolipoproteins. LAMP2 thus appears to play an important role in RPE biology, and its apparent de- crease with aging and in AMD specimens suggests that its de- ficiency may accelerate the basolaminar deposit formation and RPE dysfunction seen in these conditions.

Free Research Field

眼科

Academic Significance and Societal Importance of the Research Achievements

加齢黄斑変性は我が国における高齢者の社会的失明原因として重要である。今回の研究で、加齢黄斑変性初期病変とオートファジーの関連を検討し、網膜色素上皮細胞におけるリソソーム膜タンパクLAMP2の重要性を明らかにすることで、新たな病態モデル動物を開発した。