Identification of lead compounds to topically treat sulfur mustard injury to reduce ocular damage and improve vision.

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Project Summary The ocular surface is uniquely susceptible to Sulfur Mustard (SM) exposure, resulting in corneal lesions, edema, ulcerations, neovascularization and vision loss. Synedgen has developed a class of non-toxic polyglucosamine derivatives with the ability to suppress inflammation, reduce infection, and improve healing at mucosal surfaces. The molecules are hypothesized to act directly at the corneal surface after SM exposure to reduce the activation of downstream inflammation after primary injury, consequently reducing secondary damage, edema, neovascularization and vision loss. Synedgen's screening program uses in vitro methods to identify lead compounds to advance into animal models. Ocular residency times, distribution and tolerability in rabbits will be assessed prior to a proof-of-concept study with SM ocular exposure that uses dose and exposure time to reflect a biphasic injury that results in neovascularization and fibrosis. Monolayers of a variety of ocular epithelial cells were determined to be suitable for the high throughput screens and the first round of molecules tested met all milestones. While epithelial cells are useful for determining activity of the molecules in targeted assays, the variance in cellular response between the different cells to both stimulus and Synedgen molecules suggests that these cells independently might not predict the response of the corneal surface. To better select the best candidate molecule to advance into animal studies, this supplement proposes to use a 3D tissue model that more closely reflects the morphology and responses that expected from the human cornea.