Abstract
Purpose :
To evaluate how in vivo hyperactivation of platelet-derived growth factor receptor (PDGFR)β alters lens homoeostasis and induces epithelial-mesenchymal transition (EMT) in lens epithelial cells (LEC).
Methods :
In a mouse model of mesenchymal-specific PDGFRβ activation using the Fsp-cre transgene (herein referred to as βKI mice), lens phenotype was monitored over time. Standard histologic processing and immunohistochemistry (IHC) were used to evaluate morphologic changes and expression of PDGFRβ and α-smooth muscle actin (SMA) in the lens.
Results :
βKI mice began to develop spontaneous cataracts at 16 weeks of age while control mice did not (n=6). Histologic evaluation of lenses from βKI mice at approximately 26 weeks of age (n=6) demonstrated LEC proliferation and EMT with extracellular matrix deposition and fibrosis. By comparison, lenses from control mice were histologically normal. Expression of Fsp1-cre in LEC was confirmed using a Rosa reporter and expression of PDGFRβ in LEC was confirmed with IHC. As mice continued to age (up to 67-72 weeks; n=8), cataracts advanced and became hypermature in the βKI mice, while control lenses remained transparent. Cataractous lenses were positive for αSMA expression, as observed with IHC, while control lenses were negative. No differences in outcome measures were observed when comparing males and females.
Conclusions :
Overall, the pronounced spontaneous cataract formation in βKI mice compared to age-matched control mice, and resultant histologic changes, indicate that PDGFRβ activation is important for induction of EMT in LEC. Further, hyperactivation of PDGFRβ is a primary contributor of cataract formation.
This is a 2021 ARVO Annual Meeting abstract.