July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Immediate early genes as drivers of inflammation and posterior capsular opacification following cataract surgery
Author Affiliations & Notes
  • Samuel Novo
    Biology, University of Delaware, Silver Spring, Maryland, United States
  • Mahbubul H. Shihan
    Biology, University of Delaware, Silver Spring, Maryland, United States
  • Yan Wang
    Biology, University of Delaware, Silver Spring, Maryland, United States
  • Melinda K Duncan
    Biology, University of Delaware, Silver Spring, Maryland, United States
  • Footnotes
    Commercial Relationships   Samuel Novo, None; Mahbubul Shihan, None; Yan Wang, None; Melinda Duncan, None
  • Footnotes
    Support  NH Grant EY028597
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6447. doi:
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    • Get Citation

      Samuel Novo, Mahbubul H. Shihan, Yan Wang, Melinda K Duncan; Immediate early genes as drivers of inflammation and posterior capsular opacification following cataract surgery. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6447.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Cataract surgery is effective but acutely results in ocular inflammation. Later, remnant lens epithelial cells (LECs) undergo a wound healing response resulting in posterior capsular opacification (PCO). We reported that LECs induce pro-inflammatory gene expression by 24 hours post cataract surgery (PCS) which is 1-2 days prior to the onset of the TGF beta signaling. However, the mechanisms driving inflammatory gene expression in LECs are unknown.

Methods : Lens fiber cells were removed from adult wild-type (WT) mice to model cataract surgery and RNA isolated from LECs at 0 and 6 hours post cataract surgery (PCS), and RNAseq was conducted. The transcriptome analyses were validated by immunostaining on WT and Egr1 null mice.

Results : The expression of nearly 800 genes is altered in LECs by 6 hours PCS. Notably, while few lens or pro-fibrotic genes was changed at this short time PCS, numerous genes that modulate the innate immune response including Cox2, pentraxin 3 and Cxcl1 were upregulated. Interrogation of the gene list for transcription factors able to regulate this response revealed that several immediate early genes (IEG) encoding transcription factors were upregulated at 6 hours PCS including the most upregulated gene, FosB (124 fold), as well as Ier2, Ier3, Egr3, cFos, Atf3, Junb, and Egr1. As Egr1 regulates other lens injury responses, we investigated this molecule further. Egr1 protein is first detected in LECs at 3 hours PCS, and these levels fall by 48 hours PCS. Egr1 null LECs do not induce Cxcl1 and Cox2 expression PCS while S100a9 is still induced, indicating that Egr1 regulates a subset of the inflammatory response PCS. As Egr1 expression precedes the induction of fibrotic gene expression PCS, and inflammation is a known trigger for fibrosis, we then tested whether LECs from Egr1 null mice still undergo EMT PCS. As Egr1 null lenses still induce the expression of several fibrotic markers PCS including alpha-SMA and Tenascin-C, Egr1 appears to be nonessential for the fibrotic response of LECs PCS.

Conclusions : LECs rapidly induce IEGs PCS and this response is likely, at least in part, responsible for inflammatory responses driven by LECs post cataract surgery. However, the IEG Egr1 is not essential for the fibrotic response of LECs PCS.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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