REGULATION OF FIBROBLAST PROLIFERATION AND GENE EXPRESSION: IMPLICATIONS FOR OCULAR SURFACE FIBROSIS, SYSTEMIC INFLAMMATORY AND NEOPLASTIC DISEASE

Abstract

Pterygium is a fibrovascular proliferative disease of the ocular surface that has been linked to fibroblast proliferation and dysfunction. In my studies, profiling using microarrays found that among other significantly dysregulated non-coding RNAs, microRNA-215 and a lincRNA, linc-9432 (probe ID: A_19_P00809432) especially hold promise for further study. I showed that miR-215 was down-regulated in pterygium, and regulated fibroblast proliferation at G1 and G2 cell cycle phases through inhibition of cyclins and cell cycle-related transcripts. I validated expression levels of 24 lincRNAs found to be dysregulated in pterygium and showed that some of these have impacts on fibroblast function. Of particular interest was linc-9432, a previously unreported lincRNA, found to be down-regulated in pterygium tissue. I delineated the full sequence of linc-9432 and also suggested that it was involved in cell cycle G1 progression. These results are promising and warrant further investigation of epigenetic regulators in pterygium and other fibroblastic tissues.