Anti-angiogenic properties of a new anti-integrin protein isolated from snake venom in mouse models of choroidal neovascularization and oxygen-induced retinopathy

Abstract

Purpose: Choroidal and retinal neovascularization are common causes of blindness. Integrins play an important role in neovascular processes. Inhibition of integrins may provide an alternative to the anti-VEGF therapy of age-related macular degeneration (AMD) and ischemic proliferative retinopathy. We here evaluate in vivo the therapeutic potential of an anti-integrin protein purified from snake venom (PAIs) in the model of laser-induced choroidal neovascularization (CNV) and the oxygen-induced retinopathy (OIR).

Methods: The purified molecule was injected intravitreally in C57BL/6 mice at a dose of 56µM, on day 0, immediately after laser coagulation. The volume of laser-induced lesion was examined in vivo by spectral-domain optical coherence tomography (SD-OCT) on day 7. The area of CNV was measured, on day 8, on collagen IV and CD102 immunostained flat-mounted choroids. 7-days-old (P7) C57BL/6 pups with nursing mothers were exposed to 75% oxygen for 5 days. At P12, mice were returned to room air and injected intravitreally with PAIs at the same dose used in CNV model. At P17, vascular tufts and ischemic area were evaluated on BS-1 lectin immunostained flat-mounted retina.

Results: A single injection of PAIs significantly reduced CNV lesion volume by 32% (p<0.05) and decreased collagen IV- and CD102-positive CNV area by 34% (p<0.001) and 38% (p<0.001) respectively when compared to the non treated group. In the OIR model, PAIs significantly decreased BS-1 lectin positive-neovascular area by 50% (p<0.001).

Conclusions: Our results demonstrate that a single intravitreal injection of snake venom molecule is effective to reduce angiogenesis in a neovascular experimental AMD and in oxygen-induced retinopathy in mice.