Design of an antioxidant nanogel for corneal alkali burn treatment

Abstract

.Corneal alkali burns are a relatively common ophthalmic emergency that can seriously endanger sight. The underlying pathogenesis of these burns is driven in part by oxidative stress-related disruption of normal epithelial repair processes in the cornea and the consequent initiation of inflammatory feedback cycles that culminate in corneal neovascularization and the long-lasting or even permanent impairment of vision. Extant treatment options for such burns are limited by suboptimal efficacy and the potential for severe adverse reactions, underscoring the urgent need to develop more efficacious therapeutic alternatives. To address this issue, in this study tetramethylpiperidine (Tpl) grafted polyethyleneimine (PEI) (PEI-Tpl) and selecysteamine-astaxanthin (ATX)-selecysteamine (ASe) were cross-linked with oxidized hyaluronic acid to produce a nanogel with antioxidant properties. This nanogel preparation was capable of mitigating reactive oxygen species levels and suppressing apoptosis in corneal epithelial cells exposed to H2O2in vitro as a model of oxidative stress. Such nanogel treatment also suppressed the expression of inflammatory mediators including IL-1β, TNF-α, and IL-6 in macrophages that had been stimulated with LPS. Strikingly, in a rat alkali burn model, this nanogel was also able to satisfactorily suppress inflammation and control oxidative stress while inhibiting angiogenesis. Together, these results emphasize the promise of this novel nanogel as a tool to facilitate corneal injury repair, providing a novel therapeutic approach to the management of corneal alkali burns in the clinic.