Year: 2023
Type: review
Abstract: Neovascular eye diseases include conditions such as retinopathy of prematurity, proliferative diabetic retinopathy, and neovascular age-related macular degeneration. Together, they are a major cause of vision loss and blindness worldwide. The current therapeutic mainstay for these diseases is intravitreal injections of biologics targeting vascular endothelial growth factor (VEGF) signaling. Lack of universal response to these anti-VEGF agents coupled with the challenging delivery method underscore a need for new therapeutic targets and agents. In particular, proteins that mediate both inflammatory and proangiogenic signaling are appealing targets for new therapeutic development. Here, we review agents currently in clinical trials and highlight some promising targets in preclinical and early clinical development, focusing on the redox-regulatory transcriptional activator APE1/Ref-1, the bioactive lipid modulator soluble epoxide hydrolase, the transcription factor RUNX1, and others. Small molecules targeting each of these proteins show promise for blocking neovascularization and inflammation. The affected signaling pathways illustrate the potential of new antiangiogenic strategies for posterior ocular disease. SIGNIFICANCE STATEMENT: Discovery and therapeutic targeting of new angiogenesis mediators is necessary to improve treatment of blinding eye diseases like retinopathy of prematurity, diabetic retinopathy, and neovascular age-related macular degeneration. Novel targets undergoing evaluation and drug discovery work include proteins important for both angiogenesis and inflammation signaling, including APE1/Ref-1, soluble epoxide hydrolase, RUNX1, and others.
Institution: Indiana University School of Medicine
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,750
Awards: (PQ9)Mechanistic Role of APE1 and BER in chemotherapy-induced peripheral neuropathy, Targeting the Ref-1 signaling node for treating ocular neovascularization, (PQ12) Enhancement of DNA repair in neurons via a targeted APE1 small molecule modifier to decrease and reverse chemotherapy-induced peripheral neuropathy (CIPN), Exploiting the Ref-1 node in pancreatic cancer: tailoring new pancreatic cancer therapy using multi-targeted combinations, Ref-1 in Retinal Neovascularization, Hyperglycemia mediated myeloproliferative disease, Ferrochelatase as a mediator of ocular angiogenesis, Indiana University Melvin and Bren Simon Comprehensive Cancer Center Support Grant
OpenAlex ID: W4368341716