Angiotensin (1-7)-based Proteomimetic Polymers as Topicals for the Remediation and Repair of the Cornea following Injury
Year: 2026
Type: preprint
Abstract: The cornea is the outermost layer of the eye, most vulnerable to injury including from chemical exposure, either environmental, industrial or chemical weapons. For example, exposure of the eye to sulfur mustard (SM) can cause mustard gas keratopathy, resulting in devastating consequences for vision. Available treatments for corneal mustard keratopathy are either ineffective, or if used for a prolonged time, have deleterious side effects. Here, we aimed to harness the anti-inflammatory and anti-angiogenic peptide angiotensin-(1-7), known as Ang-(1-7), that is derived from the renin-angiotensin system (RAS). We designed and developed a protein-like polymer (PLP) displaying a brush of norleucine modified Ang (1-7) peptides (NLE Ang (1-7) PLP), which is a more potent derivative of Ang-(1-7), for administration as an eye drop. In a mouse model of nitrogen mustard (NM)-induced corneal injury, topical treatment and intraperitoneal (i.p.) injection of NLE Ang (1-7) PLP persistently minimized: (i) corneal haze; (ii) edema; (iii), expression of pro-inflammatory and pro-angiogenic genes; and (iv) neovascularization and conjunctivalization as evidenced after a prolonged treatment and recovery period. Collectively, our observations have demonstrated the efficacy of this novel polymer proteomimetic based eye drop treatment in reducing chemical agent-induced corneal injury as well as indicating its potential application in other ocular surface diseases associated with inflammation and angiogenesis.
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Science Foundation, Northwestern University, National Institutes of Health, Robert H. Lurie Comprehensive Cancer Center, National Heart, Lung, and Blood Institute, National Eye Institute, National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Division of Materials Research
Awards: G1164661550, G1284175734, G1382277591, G317886719, G322890519, G4159268500, The Role of MicroRNAs in Corneal Epithelial Homeostasis, Collaborative Research: Protein-Like Polymers: Theory and Design for Engaging Biological Interfaces, G9000046704, Northwestern University Skin Biology and Diseases Resource-based Center, MMP responsive polymeric materials for treating acute myocardial infarction, The Roles of Autophagy in Limbal/Corneal Epithelia, The Robert H. Lurie Comprehensive Cancer Center, Single-cell RNA sequencing reveals novel regulatory pathways in maintaining limbal epithelial stem cell homeostasis
OpenAlex ID: W7215969221