Abstract
Purpose :
The purpose of this study was to evaluate the anti-inflammatory and anti-oxidant effect of Risuteganib® on an experimental Dry Eye Model (DED) on young C57BL/6J female mice. Risuteganib® is a first-in-class integrin-inhibitor and has been shown to have treatment effects for both vitreolysis and angiogenesis. Proteomics and genomic testing at Caltech have suggested a potential neuroprotective effect, however, its anti-inflammatory and antioxidant effects on dry eye have not been previously reported.
Methods :
The dry eye was induced by exposing C57BL/6 mice to desiccating stress using a controlled environment chamber for 12 days. Experimental groups receive scopolamine injection.
Animals
Animal handling was approved by the Institutional Animal Care and Use Committee, which adheres to the national law and NIH rules. Young (2-month-old) female C57BL/6J mice were maintained on a 12h light/dark cycle in a temperature controlled room.
Experimental design
Sixteen mice (four mice per group) were used in each experiment in four experimental conditions: No desiccating stress conditions and no scopolamine (Control-), No desiccating stress conditions and scopolamine (Control+), Scopolamine + Saline (SSB) + desiccating conditions (1 drop each 12 hours along 12 days, and scopolamine + vehicle + desiccating stress + Risuteganib® (1 drop each 12 hours along 12 days ).
Double immunofluorescence assays
Corneal slices from each group were processed and stored until use for immunohistochemistry for IL-1β, IL-6, TNF-alpha, GFAP, 18 kDa translocator protein (TSPO), caspase 6 and 9, Superoxide dismutase (SOD), glutathione peroxidase and catalase.
Results :
Risuteganib® reduced corneal levels of pro-inflammatory cytokine interleukin-1β(IL-1β), IL-6, TNF-alpha, Glial acidic fibrillary protein (GFAP) and (TSPO) as well as, caspase 6 and 9 and increase the expression of (SOD), glutathione peroxidase and catalase in corneal epithelium in DED experimental model.
Conclusions :
To the best of our knowledge, this is the first report describing the corneal anti-inflammatory effect of Risuteganib® in a Dry Eye Disease experimental model on young C57BL/6J mice. Our results suggest the potential new use for Risuteganib®.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.