Generation of dry age-related macular degeneration model mouse and elucidation of the pathogenesis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25713056
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Nagoya University
• Principal Investigator: Kaneko Hiroki 名古屋大学, 医学(系)研究科(研究院), 助教 (20647458)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 加齢黄斑変性 / 脈絡膜新生血管 / 不飽和脂肪酸 / malondialdehyde / アミロイドβ / ヒスタミン受容体H4 / プラズマ照射液 / リノール酸

Outline of Final Research Achievements

Amyloid β induced vascular endothelial growth factor (VEGF) and endoplasmic reticulum (ER) stress marker up-regulation in retinal pigment epithelium (RPE). ER stress inhibitor blocked VEGF secretion. When large amount of linoleic acid was administered in mice, malondialdehyde (MDA) was accumulated in RPE and blood. MDA was also detected in the RPE and blood from the patients with AMD. In the administration of MDA in cultured human RPE cells, low concentrations of MDA induced VEGF up-regulation without inducing RPE damage, whereas high concentrations of MDA induced VEGF down-regulation and RPE degeneration. This change suggested the difference of wet- and dry-AMD.
We verified the expression of histamine receptor H4 (HRH4) in the choroidal neovascularization (CNV) and the vitreous injection or oral administration of the anti-HRH4 medicine reduced CNV. Plasma-activated medium irradiated with low temperature plasma also reduced CNV in mice.

Free Research Field

網膜硝子体疾患