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Fabian Garreis, Eva Beckenbauer, Ulrike Schulte, Martin Schicht, Ulrike Hampel, Friedrich P Paulsen; Influence of psoriasin on VEGF-mediated corneal neovascularization. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5082.
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The S100 peptide psoriasin (S100A7) shows a broad antimicrobial activity and is part of the innate immune defense system of the ocular surface. Moreover, psoriasin is induced by VEGF and contributes to increased angiogenesis and proliferation of various tumor cells. VEGF-induced corneal neovascularization (CNV) is associated with a decrease in vision and can ultimately lead to blindness. The influence of psoriasin on CNV is unknown and was analyzed in the present study.
Expression of tear S100 proteins like psoriasin, hornerin and calprotectin was analyzed in cornea sections from various ocular surface diseases by immunohistochemistry. Cell culture experiments were used to investigate the impact of psoriasin, VEGF, soluble receptor for advanced glycation end products (sRAGE), H2O2 and siRNA-mediated knockdown of psoriasin on human corneal epithelial (HCE-cell line) cells. Changes to expression of psoriasin-dependent factors were analyzed by qPCR, western blot as well as ELISA experiments. Additionally, the impact of psoriasin, VEGF and sRAGE on proliferation and the formation of reactive oxygen species (ROS) were determined by functional assays.
Compared to healthy tissue, there were no visible changes of psoriasin expression in cornea sections from various ocular surface diseases. Stimulation of cultivated HCE cells with VEGF and sRAGE increased the psoriasin expression at the mRNA level. Gene expression of VEGF was significantly increased whereas VEGF receptor-1 was reduced after application of recombinant psoriasin. Expression of the potential psoriasin receptor RAGE was significantly increased by different VEGF concentrations whereas psoriasin led to a reduction of RAGE. HCE cells revealed a significant increase in cell viability and an increased ROS formation after stimulation with VEGF, psoriasin and low H2O2 concentrations. In contrast, psoriasin knockdown by siRNA resulted in a reduced proliferation of HCE cells and an increased production of ROS.
Based on our preliminary results in HCE cells a dose-response effect of psoriasin on ROS production and cell viability is detectable and indicate an involvement of psoriasin in VEGF-mediated cellular processes in these cells. Further analyses are necessary to reach a final conclusion on the impact of psoriasin to VEGF-mediated CNV and to contribute a novel approach to inhibit VEGF-induced CNV.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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