Preclinical Efficacy of Pro- and Anti-Angiogenic Peptide Hydrogels to Treat AMD

Summary: Pro-angiogenic and anti-angiogenic peptide hydrogels were evaluated against the standard of care wet AMD therapy, Aflibercept, in a rat laser-induced CNV model. Efficacy was determined over 14 days via FA and SD-OCT.

The Department of Biomedical Engineering, New Jersey Institute of Technology, Stanford School of Medicine at Stanford University, the Department of Biology at the New Jersey Institute of Technology, the Cole Eye Institute at the Cleveland Clinic Lerner College of Medicine, the Department of Chemical Engineering at the New Jersey Institute of Technology, the Department of Restorative Dentistry at Rutgers School of Dental Medicine, the Department of Ophthalmology at Loyola University Chicago, and Experimentica’s Research & Development Division in Kuopio, Finland, published about the preclinical efficacy of pro- and anti-angiogenic petide hydrogels to treat AMD in Bioengineering.

Pro-angiogenic and anti-angiogenic peptide hydrogels were evaluated against the standard of care wet age-related macular degeneration (AMD) therapy, Aflibercept (Eylea®).

AMD was modeled in rats (laser-induced choroidal neovascularization (CNV) model), where the contralateral eye served as the control. After administration of therapeutics, vasculature was monitored for 14 days to evaluate leakiness. Rats were treated with either a low or high concentration of anti-angiogenic peptide hydrogel (0.02 wt% 8 rats, 0.2 wt% 6 rats), or a pro-angiogenic peptide hydrogel (1.0 wt% 7 rats). As controls, six rats were treated with commercially available Aflibercept and six with sucrose solution (vehicle control). Post lasering, efficacy was determined over 14 days via fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). Before and after treatment, the average areas of vascular leak per lesion were evaluated as well as the overall vessel leakiness.

Unexpectedly, treatment with pro-angiogenic peptide hydrogel showed significant, immediate improvement in reducing vascular leak; in the short term, the pro-angiogenic peptide performed better than anti-angiogenic peptide hydrogel and was comparable to Aflibercept. After 14 days, both the pro-angiogenic and anti-angiogenic peptide hydrogels show a trend of improvement, comparable to Aflibercept.

Based on our results, both anti-angiogenic and pro-angiogenic peptide hydrogels may prove good therapeutics in the future to treat wet AMD over a longer-term treatment period.

Authors:  Amanda Acevedo-Jake | Siyu Shi | Zain Siddiqui | Sreya Sanyal | Rebecca Schur | Simon Kaja | Alex Yuan | Vivek A. Kumar

Keywords: wet age-related macular degeneration; pro-angiogenic; anti-angiogenic; hydrogel; biomaterials; tissue regeneration; multi-functional scaffolds