光暴露による網膜細胞死のメカニズムには酸化ストレスが含まれることは報告されているが, その分子メカニズムには未だ不明の点が多い。そこで, 光障害による視細胞死のメカニズムを分子レベルで解析した。その結果, レニン・アンジオテンシン系抑制剤の投与がそれを抑制することを示した。すなわち, レニン・アンジオテンシン系抑制剤の投与が網膜内の酸化ストレスを抑制すると共に, アポトーシスシグナルを抑制し, c-fos等の鍵となる分子の発現抑制を示した。
We examined the role of angiotensin II type 1 receptor (AT1R) signaling, which is part of the renin-angiotensin system, in light-induced retinal damage. Light-exposed Balb/c mice that were treated with the AT1R blockers (ARBs) before and after the light exposure exhibited attenuated visual function impairment, compared to vehicle-treated mice. Further evaluation of an ARB, valsartan, showed that it suppressed a number of light-induced retinal effects, including thinning of the photoreceptor cell layer caused by apoptosis, shortening of the photoreceptor cell outer segment, and increased levels of reactive oxygen species (ROS). The ARB suppressed the induction of c-fos and the upregulation of fasl after light exposure. Our results suggest that AT1R signaling mediates light-induced apoptosis, by increasing the levels of ROS and proapoptotic molecules in the retina. Thus, AT1R blockade may represent a new therapeutic approach for preventing light-induced retinal neural damage.
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