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Samuel G Novo, Ananya Garg, Adam Faranda, Mahbubul H. Shihan, Yan Wang, Melinda K Duncan; Transcription factors mediating the post cataract surgery response. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2791.
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Cataract surgery is known to induce ocular inflammation, which if left untreated, can result in damage to other ocular tissues. We have previously reported that the lens epithelial cells (LECs) retained in the eye post cataract surgery (PCS) initiate the expression of inflammatory cytokines 1-2 days prior to their phenotypic transition into the myofibroblasts and aberrant lens fiber cells that cause posterior capsular opacification (PCO). However, the mechanism driving the initiation of inflammatory gene expression in LECs and its relationship to PCO pathogenesis is unknown.
RNA isolated from wildtype (WT) mouse LECs at 0 and 6 hours after lens fiber cells removal to simulate cataract surgery was used for RNAseq. FosBtm1.Nes mice that carry a floxed FosB allele were bred to MLR10Cre mice, which express Cre recombinase in the lens, to generate a FosB lens conditional knockout (cKO) mice. RNAseq was conducted on the FosB cKO mice similarly to the wildtype (WT) mice. The transcriptomic changes observed were validated by immunostaining WT and FosB cKO mice at various times PCS.
RNAseq revealed that remnant LECs upregulate numerous genes known to contribute to the inflammatory response, smooth muscle cell proliferation, and cell migration by 6 hours PCS. Further, the top most upregulated differentially expressed gene in LECs at 6 hours PCS was FosB, a member of the AP1 complex of transcription factors and an immediate early gene (IEG), which drives the inflammatory, fibrotic, and proliferation response of cells in other systems. FosB protein levels upregulate in LECs by 6 hours PCS and slowly downregulate over the next 5 days PCS. We generated a FosB lens cKO mouse to test the hypothesis that FosB upregulation PCS is important in LEC response to surgery. These lenses develop normally and are transparent into adulthood. Initial analysis of the upregulation of TNC, a classic fibrotic marker, and CXCL1 and COX2, 2 classic inflammatory markers, did not reveal any major changes, however, RNAseq is ongoing to determine globally the role of FosB PCS.
IEGs, including FosB upregulate robustly within 6 hours PCS. FosB is not necessary for lens development or transparency, while its roles in PCO are under active investigation.
This is a 2021 ARVO Annual Meeting abstract.
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