Friday, April 26, 2024
4/26/2024
Abstract Chemical burns to the eye are potentially blinding ocular injuries and constitute an ocular emergency requiring immediate assessment and initiation of treatment. They also constitute between 7-10% of the eye injuries in the general population. Out of all chemical injuries, alkali injuries are the most common and the most deleterious. Recurrent epithelial erosions, severe stromal inflammation, neovascularization, corneal ulceration and perforation are all prevalent complications of alkali burns. Currently, there is no successful treatment for severe damage to the cornea or to maintain corneal transparency. This proposal builds upon our previous findings that the lipid mediator, lipoxin A4 (LxA4), stimulates epithelial and endothelial wound healing, is involved in the reparative action of epidermal growth factor, and inhibits the inflammatory response stimulated after corneal injury. In addition, after severe alkali burn, there is a shortage of repair fibroblasts in ulcerated corneas, which is needed to synthesize components of the extracellular matrix (ECM) and to repair the stroma. The organizing hypothesis of the proposed research is that controlling the intense inflammatory response with LxA4 and reconstituting the ECM by stromal cell transplantation in a severe alkali burn model will avoid ulceration and neovascularization, thereby improving the visual outcome after severe ocular chemical injuries. We will test this hypothesis by pursuing two specific aims. In Specific Aim 1, we will use a severe rat alkali burn model (both sexes) to assess the action of LxA4 in in vivo clinical parameters and in inflammatory cytokines and conversion of macrophages type 1 (M1) to M2 by flow cytometry and immunofluorescence. In Specific Aim 2, we will investigate the anti-inflammatory action of the limbal stromal cells and combine treatment with LxA4 defined in Specific Aim 1 with cell transplantation of repair fibroblasts in the rat alkali burn model. We will determine clinical scores, presence of inflammatory cells, and ECM components after an early (3 days) and late (5 days) cell transplantation. The proposed studies, if successful, will target new approaches to investigate a novel treatment to control intense inflammation, to preserve the globe, and possibly, to restore transparency.
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