Allosteric regulation of pathologic angiogenesis: potential application for angiogenesis-related blindness

Abstract

Angiogenesis-related blindness (ARB) includes age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity, all of which are based on pathologic angiogenesis. Current treatment options such as surgery, laser photocoagulation, and steroid have shown limitations because they do not directly resolve the pathologic events in the retina. Furthermore, recently approved and developed therapeutic drugs only focus on direct inhibition of growth factors and suppression of downstream signaling molecules of activated receptor proteins by orthosteric ligands. In this regard, allosteric regulation of receptors and ligands can be a valuable mechanism in the development of novel drugs for ARB. In this review, we briefly address the clinical significance of ARB for further discussion on allosteric regulation of pathologic angiogenesis for ARB. Interestingly, key molecules in the pathogenesis of ARB can be targets for allosteric regulation, sharing characteristics as allosteric proteins. With investigation of allostery by introducing well-established models for allosteric proteins and currently published novel allosteric modulators, we discuss the potential of allosteric regulation for ARB. In conclusion, we hope that allosteric regulation of pathologic angiogenesis in ARB can open new opportunities for drug development.