The role of pigment production of retinal pigment epithelium in the pathogenesis of age-related macular degeneration.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18389
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Nara Medical University
• Principal Investigator: Hiroki Tsujinaka 奈良県立医科大学, 医学部, 学内講師 (50596749)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 加齢黄斑変性 / 網膜色素上皮 / 喫煙 / ブルーライト

Outline of Final Research Achievements

Abnormal pigmentation or depigmentation of the retinal pigment epithelium (RPE) is a known precursor lesion of Neovascular age-related Macular degeneration (nAMD). We evaluated the effect of Hydroquinone (HQ) on melanin production using RPE cells. iPS - derived RPE and ARPE-19 cells were cultured with HQ. Realtime RT-PCR revealed that the expression of melanin-related production genes was signifi-cantly decreased by the addition of HQ for 1 day. The absorbance of RPE suspension was de-creased, especially in the blue light. On the other hand, melanin expression was significantly in-creased after the addition of HQ for 1 week. After the blue light irradiation, VEGF in the RPE medium was significantly higher with HQ for 1 week than the control group. HQ-induced changes in melanin production may be responsible for the uneven pigmentation of RPE.It was suggested that uneven melanin levels in RPE may affect VEGF production and influence the development of nAMD.

Free Research Field

網膜疾患

Academic Significance and Societal Importance of the Research Achievements

加齢黄斑変性は、中途失明の原因として社会的に大きな問題となっており、あらたな治療法が模索されている疾患でもある。これまで、加齢黄斑変性の発症に、網膜色素上皮細胞の色素むらが前駆病変として指摘されていたが、その原因や、病態における役割は不明であった。今回、色素上皮のむらによって、加齢黄斑変性の発症要因となるVEGFの発現量が変化することを突き止めたことは、病態解明にとって大きな意味を持つと考えらえる。色素上皮のむらを解消するための薬剤や、治療法がみつかれば、加齢黄斑変性の発症そのものを抑制できる可能性を秘めており、今後、これらの薬剤が加齢黄斑変性抑制のブレイクスルーになるかもしれない。