Title:Hypoxia-Inducible Factor-1 (HIF-1): A Potential Target for Intervention in Ocular Neovascular Diseases
Volume: 14
Issue: 8
Author(s): Ramya Krishna Vadlapatla, Aswani Dutt Vadlapudi and Ashim K. Mitra
Affiliation:
Keywords:
Age-related macular degeneration, diabetic retinopathy, hypoxia signaling, hypoxia-inducible factor-1 (HIF-1),
ocular neovascularization, retinopathy of prematurity.
Abstract: Constant oxygen supply is essential for proper tissue development, homeostasis and function of all eukaryotic
organisms. Cellular response to reduced oxygen levels is mediated by the transcriptional regulator hypoxia-inducible factor-
1 (HIF-1). It is a heterodimeric complex protein consisting of an oxygen dependent subunit (HIF-1α) and a constitutively
expressed nuclear subunit (HIF-1β). In normoxic conditions, de novo synthesized cytoplasmic HIF-1α is degraded
by 26S proteasome. Under hypoxic conditions, HIF-1α is stabilized, binds with HIF-1β and activates transcription of
various target genes. These genes play a key role in regulating angiogenesis, cell survival, proliferation, chemotherapy,
radiation resistance, invasion, metastasis, genetic instability, immortalization, immune evasion, metabolism and stem cell
maintenance. This review highlights the importance of hypoxia signaling in development and progression of various vision
threatening pathologies such as diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration
and glaucoma. Further, various inhibitors of HIF-1 pathway that may have a viable potential in the treatment of oxygendependent
ocular diseases are also discussed.
