Inhibition of the HIF-1α/BNIP3 pathway has a retinal neuroprotective effect

Hiromitsu Kunimi, Deokho Lee, Mari Ibuki, Yusaku Katada, Kazuno Negishi, Kazuo Tsubota, Toshihide Kurihara

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Retinal ischemia is a leading cause of irreversible blindness worldwide. Inner retinal dysfunction including loss of retinal ganglion cells is encountered in a number of retinal ischemic disorders. We previously reported administration of two different hypoxia-inducible factor (HIF) inhibitors exerted neuroprotective effects in a murine model of retinal ischemia/reperfusion (I/R) which mimics these disorders, as inner retinal degeneration could be involved in pathological HIF induction. However, this notion needs further investigation. Therefore, in this study, we attempted to use retina-specific Hif-1α conditional knockout (cKO) mice to uncover this notion more clearly under the same condition. Hif-1α cKO mice showed inner retinal neurodegeneration to a lesser extent than control mice. Hif-1α depletion in a murine 661W retinal cell line reduced cell death under pseudohypoxic and hypoxic conditions. Among hypoxia-related genes, the expression of BCL2 19 kDa protein-interacting protein 3 (Bnip3) was substantially upregulated in the inner retinal layer after retinal I/R. In this regard, we further examined Bnip3 depletion in retinal neurons in vitro and in vivo and found the similar neuroprotective effects. Our results support the notion that the HIF-1α/BNIP3 pathway may have a critical role in inner retinal neurodegeneration, which can be linked with the development of new promising therapeutics for inner retinal ischemic disorders.

本文言語English
論文番号e21829
ジャーナルFASEB Journal
35
8
DOI
出版ステータスPublished - 2021 8

ASJC Scopus subject areas

  • バイオテクノロジー
  • 生化学
  • 分子生物学
  • 遺伝学

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