Hypoxia-inducible factor-1α: A promising therapeutic target for vasculopathy in diabetic retinopathy
Abstract
Diabetic retinopathy (DR) is a serious condition that can cause blindness in diabetic patients. It is a neurovascular disease, but the pathogenesis leading to the onset of this disease is still not completely understood. However, hypoxia with subsequent neovascularization is a characteristic phenomenon observed with DR. Cellular response to hypoxia is mediated by the transcriptional regulator hypoxia-inducible factor (HIF). Long-term research has shown that one isotype of HIF, HIF-1α, may play a pivotal role under hypoxic conditions, and an increasing number of studies have shown that HIF-1α and its target genes contribute to retinal neovascularization. Therefore, targeting HIF-1α may lead to more effective DR treatments. This review describes the possible mechanisms of HIF-1α in neovascularization of DR. Furthermore, various inhibitors of HIF-1α that may have viable potential in the treatment of DR are also discussed.
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Pathological HIF activation plays a key role in diabetic complications including nephropathy, retinopathy, and impaired wound healing, largely by driving aberrant angiogenesis, fibrosis, and vascular dysfunction.
“In parallel, pathological HIF activation plays a key role in diabetic complications, including nephropathy, retinopathy, and impaired wound healing, largely by driving aberrant angiogenesis, fibrosis, and vascular dysfunction in hypoxic and inflamed tissues [26,232,247].”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [26]
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Regulation of the HIF switch in human endothelial and cancer cells
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HIF inhibition: Current strategies and clinical challenges
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“In parallel, pathological HIF activation plays a key role in diabetic complications, including nephropathy, retinopathy, and impaired wound healing, largely by driving aberrant angiogenesis, fibrosis, and vascular dysfunction in hypoxic and inflamed tissues [26,232,247].”
- Authors
- Li, H.-Y., Yuan, Y., Fu, Y.-H., Wang, Y., & Gao, X.-Y.
- Affiliations
- Harbin Medical University (CN)
- ORCID
- Yuan, Yue
- Venue
- Pharmacological Research
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 159
- Pages
- 104924
- ISSN
- 1043-6618 (ISSN-L)
- OpenAlex
- W3027314404
- Cited by
- 88
- References
- 11
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 15 · 2023: 12 · 2022: 15 · 2021: 10 · 2020: 2
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacological Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Foundation of Heilongjiang Province (H2015057)
- Postgraduate Research & Practice Innovation Program of Harbin Medical University (YJSSJCX2019-15HYD)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- hypoxia-inducible factor-1α, diabetic retinopathy, retinal neovascularization, hypoxia, therapeutic target, HIF-1α inhibitors, neurovascular disease, retinal vascular disease
- MeSH terms
- Animals, Diabetic Retinopathy, Gene Expression Regulation, Humans, Neovascularization, Pathologic, Protein Conformation, Structure-Activity Relationship, Signal Transduction, Angiogenesis Inhibitors, Vascular Endothelial Growth Factor A, Hypoxia-Inducible Factor 1, alpha Subunit
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