| First Author | Kunimi H | Year | 2021 |
| Journal | FASEB J | Volume | 35 |
| Issue | 8 | Pages | e21829 |
| PubMed ID | 34314069 | Mgi Jnum | J:321382 |
| Mgi Id | MGI:6741317 | Doi | 10.1096/fj.202100572R |
| Citation | Kunimi H, et al. (2021) Inhibition of the HIF-1alpha/BNIP3 pathway has a retinal neuroprotective effect. FASEB J 35(8):e21829 |
| abstractText | 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-1alpha conditional knockout (cKO) mice to uncover this notion more clearly under the same condition. Hif-1alpha cKO mice showed inner retinal neurodegeneration to a lesser extent than control mice. Hif-1alpha 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-1alpha/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. |
