Investigation of effect of Rho kinase inhibitor on retina and ocular surface for clinical application.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20302
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Tohoku University
• Principal Investigator: Yokoyama Yu 東北大学, 大学病院, 助教 (00597312)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 緑内障 / 神経保護 / Rho kinase阻害薬 / K115 / リパスジル

Outline of Final Research Achievements

In the present study,I examined whether K115 eye drop administration could provide a neuroprotective effect in an optic nerve crush model in mice. For assessment of neuroprotection, the retinal thickness were measured by OCT and quantification of retinal ganglion cell marker using PCR were performed 7 days after optic nerve crush in mice which were administrated K115. As a result, no clear neuroprotective effect was observed. Next, when the retinal ganglion cell protective effect was examined in intravitreal administration, the protective effect by K115 was observed.
The changes in Iba-1 positive cells and the expression of inflammatory cytokines by qPCR were examined in nerve crash model with K115 administration, on the hypothesis that the anti-inflammatory effect of K115 is related to neuroprotection. Although K115 administration changed the expression of some inflammatory cytokines, the anti-inflammatory effect was not clear.

Free Research Field

神経保護

Academic Significance and Societal Importance of the Research Achievements

緑内障はそのRGCの不可逆的障害によって生じる失明疾患で眼圧下降治療以外のエビデンスに基づいた治療法はない。
本研究では抗緑内障薬として使用されるリパスジル（K115）の持つ神経保護薬としての効果を検証した。本研究でK115硝子体内投与によりマウスの視神経軸索挫滅モデルで神経保護効果を確認することができた。K115の持つ抗炎症作用が神経保護に関与するという仮説を立てて、Iba-1陽性細胞の変化と炎症性サイトカインの発現を検証した。K115投与でいくつかの炎症性サイトカインの発現に変化をみとめたが抗炎症作用ははっきりしなかった。K115の持つ神経保護効果の検証にはさらに研究が必要と思われた。