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Imane ASSAKHI, Yan Wang, Melinda K Duncan, Mahbubul H Shihan, Adam P Faranda; The function of α5β1-integrin in fibrotic PCO. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5034.
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© ARVO (1962-2015); The Authors (2016-present)
Cataract surgery results in excellent visual outcomes. However, the lens epithelial cells remaining behind post cataract surgery (PCS) can proliferate and enter the visual axis resulting in posterior capsular opacification (PCO). We found that fibronectin, an extracellular matrix protein, plays multifunctional roles in PCO pathogenesis, although the relative contribution of each function is unclear. Here, we study the role that α5β1-integrin, the canonical fibronectin receptor, plays in PCO development.
RNAseq and immunostaining were used to discover the time course of α5β1 expression post cataract surgery (PCS) in a mouse model. Itga5tm2Hyn mice which carry a floxed a5 integrin allele were bred to MLR10Cre mice which express Cre recombinase in the lens to create α5cKO mice. Cataract surgery is performed on both WT and α5cKOs mice, eyes collected at different time points PCS, and the wound healing phenotype analyzed by immunolocalization.
RNAseq found that α5 integrin mRNA levels increase in remnant lens epithelial cells (LECs) by 6h PCS, while β1 integrin mRNA levels do not change until 24 hours PCS. Immunostaining found that a5 integrin protein levels are low in unoperated lenses, but are highly elevated at 48 hours PCS and remain high at 5 days PCS. Immunostaining revealed the near complete loss of a5 integrin protein in α5cKO LECs suggesting that itga5 gene deletion was complete. While WT mice exhibit a massive increase in LEC number by 5 days PCS, this did not occur in α5cKO mice. Further, while robust α-SMA expression is seen in WT LECs by 5 days PCS, this induction of α-SMA expression was absent in α5cKO mice. Similarly, high levels of tenascin C deposit around remnant WT lens cells by 5 days PCS, but this response is greatly attenuated in α5cKO lens cells.
Many of fibronectin’s functions in fibrotic PCO pathogenesis appear to be mediated through its binding to α5β1-integrin. Thus, α5β1-integrin antagonists may be efficacious in preventing fibrotic PCO.
This is a 2020 ARVO Annual Meeting abstract.
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