Abstract
Purpose :
Cataracts are effectively treated by cataract surgery, but this is followed by ocular inflammation which is unpleasant for patients and can damage other ocular tissues. Later, remnant lens epithelial cells (LECs) convert to myofibroblasts which can cause posterior capsular opacification (PCO). We found that remnant LECs express pro-inflammatory genes by 24 hours post cataract surgery (PCS) which presages the TGF-b signaling driving PCO by 1-2 days. However, the mechanisms driving the induction of inflammatory gene expression in LECs, and their relationship to PCO pathogenesis are unknown.
Methods :
RNAseq was conducted on RNA isolated from wildtype mouse LECs at 0 and 6 hours after lens fiber cells removal which simulates cataract surgery. The transcriptomic changes observed were validated by immunostaining of WT and EGR1 null mouse (B6N;129-EGR1tm1Jmi/J) eyes at various times after lens fiber cell removal. 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. Additionally, immunostaining was conducted PCS to determine expressional gene differences in cKO to WT mice.
Results :
Over one-tenth of the top 50 differentially expressed genes in LECs at 6 hours PCS were immediate early genes (IEGs) which can drive the innate immune response, fibrosis and cell proliferation. FosB, the most upregulated gene at 6 hours PCS, and EGR1, one of the highest expressed IEGs induced at 6 hours PCS (364 FPKM), are both upregulated in LECs at the protein level by 3 hours PCS. As FosB regulates inflammation via COX2 transcription and fibrosis through tenascin C transcription in other systems, the FosB gene was removed from the lens, and it does not appear to be needed for lens development. EGR1 null lenses are also grossly normal, but they show attenuated inflammatory regulator expression and some attenuated fibrotic marker expression PCS.
Conclusions :
Cataract surgery induces LECs to upregulate IEG expression, which may be responsible for the induction of ocular inflammation and initiation of the epithelial to mesenchymal transition of LECs PCS.
This is a 2020 ARVO Annual Meeting abstract.