Preclinical Efficacy of Pro- and Anti-Angiogenic Peptide Hydrogels to Treat Age-Related Macular Degeneration

Abstract

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.

Self-Assembling Peptides with Insulin-Like Growth Factor Mimicry

“…Prior work from our group and others has shown that these characteristic SAP nanofibers have dimensions similar to those of selfassembled peptides with distinct mimic architectures (angiogenic, neurogenic, etc.). [14][15][16]23,34,38 Rheometric Analysis of Constructs. Oscillatory rheometric analysis was performed on the peptide hydrogels (Figure 3A 3E,F).…”

“…18−21 Therefore, we adopted our biodegradable and benchmarked SAP scaffolds for generation of synthetic growth factors. 22,23 We optimized the SAP-IGF-1 mimic sequence and spacer domains and further studied IGFR binding using in silico analyses, upregulation of the IGF-1/IGFR-activated and proangiogenic Akt signaling pathway in vitro, and angiogenesis within cytocompatible, biocompatible, and biodegradable scaffolds in vivo.…”

“…We have previously described a proangiogenic SAP rationally designed from VEGF-A . Similarly, the Yang group has described an IGF mimic of the mid-C domain of IGF-1 that upregulates intracellular signaling alone or when conjugated to a naphthalene backbone with a therapeutic effect in rodent models of hind limb ischemia revascularization, muscle fiber thickening in glucocorticoid-induced sarcopenia, and spinal cord injury recovery. − Therefore, we adopted our biodegradable and benchmarked SAP scaffolds for generation of synthetic growth factors. , We optimized the SAP-IGF-1 mimic sequence and spacer domains and further studied IGFR binding using in silico analyses, upregulation of the IGF-1/IGFR-activated and proangiogenic Akt signaling pathway in vitro, and angiogenesis within cytocompatible, biocompatible, and biodegradable scaffolds in vivo.…”

Applications and Recent Developments of Hydrogels in Ophthalmology

“…The binding of antiangiogenic active molecules to the hydrogel skeleton is also an attractive topic of study. Acevedo-Jake et al grafted antivascular peptides onto self-assembled peptides to form antiangiogenic polypeptide hydrogels 92 (Figure 5A). In a rat choroidal neovascularization model, the antiangiogenic polypeptide hydrogel showed an improvement trend after 14 days of treatment, which was similar to that of Aflibercept.…”

“…(A) Schematic of the proposed assembly mechanism of the hydrogels. Reproduced with permission from ref . Copyright 2021 MDPI.…”