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Abstract #53775 Published in IGR 15-2
Hypoxia-Inducible Factor-1 (HIF-1): A Potential Target for Intervention in Ocular Neovascular Diseases
Vadlapatla RK; Vadlapudi AD; Mitra AKCurrent Drug Targets 2013; 14: 919-935
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.
University of Missouri- Kansas City, School of Pharmacy, 2464 Charlotte Street, Kansas City, MO 64108-2718, USA.mitraa@umkc.edu.
Classification:
3.8 Pharmacology (Part of: 3 Laboratory methods)
6.11 Bloodflow measurements (Part of: 6 Clinical examination methods)
3.6 Cellular biology (Part of: 3 Laboratory methods)
