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Pierfrancesco Mirabelli, Anthony Mukwaya, Anton Lennikov, Maria Xeroudaki, Beatrice Peebo, Neil S Lagali; Topical steroids vs anti-Vegf in experimental corneal neovascularization: differential efficacy, microscopic features and genomic response. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1011. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Pathologic angiogenesis is involved in cancer and several blinding conditions, like wet AMD, proliferative retinopathies and corneal neovascularization. Among available treatments, anti-VEGF often shows limited efficacy, while steroids are potentially responsible for many side-effects. We performed a series of linked studies to assess the efficacy of topical dexamethasone relative to anti-VEGF in a corneal model of experimental neovascularization, and the effect on microscopic features in vivo and on gene expression.
Male Wistar rats were sutured intrastromally in right corneas 1.5 mm from the temporal limbus. Thereafter, treatment was given with dexamethasone, rat specific anti-Vegf, or goat IgG (control), topically QID for 2-7 days. Slit lamp photography to assess and quantify macroscopic vessel growth, and in vivo confocal microscopy to study cell infiltration and limbal vessel dilation, and detect microscopic vessel sprouts, were performed longitudinally. Genomic analysis with RNA Microarray, selected gene expression with q-RTPCR, and selected protein expression in tissue (immunohistochemistry, immunofluorescence, western blot) were performed at 48 hours, during the early pre-sprouting phase.
At day 7, dexamethasone suppressed corneal neovascularization more than anti-Vegf (90% vs. 14%). No difference was detectable concerning cell infiltration on IVCM at 48 hours, but only dexamethasone inhibited limbal vessel dilation (p < 0,01). Microarray at 48 hours showed that in dexamethasone treated cornea 511 fewer genes were differentially expressed relative to naïve corneas, compared to anti-Vegf and IgG. Among the differentially expressed genes, several major and novel angiogenic and pro-inflammatory factors and chemokines were suppressed only by dexamethasone.
More effective treatments of corneal inflammation and neovascularization with less side-effects are needed. In this study several potential novel factors and mechanisms are identified that are not addressed by anti-VEGF therapy, and therefore represent interesting targets for further study.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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