Abstract
Purpose :
Integrins are heterodimeric extracellular matrix (ECM) receptors consisting of one α- and one β-integrin subunit which play a major role in cell proliferation, adhesion, migration, differentiation and apoptosis. Our lab already demonstrated that αV-integrins are essential for the robust proliferation of residual lens epithelial cells (LECs) and development of fibrotic posterior capsular opacification (PCO) following lens fiber cell removal (Mamuya et al, 2014). Since each heterodimer has a different ligand binding profile/function and is inhibited by different compounds, the identification of the β-integrin that functions with αV-integrin is critical to the development of anti-PCO therapies. Our preliminary data indicated that αV-integrin and its interacting β-subunits; β1, β5, β6, β8 along with α-smooth muscle actin (αSMA) are upregulated 48hrs post cataract surgery in mice. Of these, the β5-integrin subunit is the most robustly upregulated β-integrin after fiber cell removal in mice while other studies have shown that αVβ6-integrin can activate transforming growth factor beta. Thus, we hypothesized that αVβ5 and/or αVβ6-integrin are the crucial regulators of fibrotic PCO.
Methods :
Homozygous β5 and β6-integrin null mice were generated and eyes were characterized. The lens fiber cells removed to model cataract surgery and capsular bags were then collected at 0 hr, 48 hrs and 5 days post-surgery for PCO development. Immunostaining was done to see the expression pattern of epithelial mesenchymal transition (EMT) markers and fibrotic markers including αSMA.
Results :
At o hr and 48 hr post-surgery, we have seen little to no upregulation of αSMA expression in both β5- integrin and wildtype lenses. However, β5-integrin null lenses show robust upregulation of αSMA expression at 5 days post-surgery which is similar compared to wild type lenses.
Conclusions :
Our preliminary data suggests that αVβ5 is not solely required for fibrotic responses. It is possible that αVβ6 or a combination of αVβ5 and αVβ6 is required to regulate fibrotic PCO. We are currently working on β6- integrin null mice to find out the role of β6- integrin in the development of PCO.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.