Abstract
Purpose :
Cataract is treated by extracapsular lens extraction, but retained lens epithelial cells (LECs) proliferate, migrate, and undergo epithelial to mesenchymal transition leading to posterior capsular opacification (PCO) that compromises vision months to years post-surgery. Comprehensive RNAseq profiling revealed that Thrombospondin-1 (THBS1), an ECM regulator known to play roles in TGF-β-mediated fibrosis in other systems, upregulates its expression in LECs after lens fiber cell removal in an animal model. This study tests THBS1 function in the lens injury response.
Methods :
Thbs1 null mice (B6.129S2-Thbs1tm1Hyn/J) were obtained from Jackson Laboratory and their lens phenotype explored by slit lamp, dark field imaging and hematoxylin and eosin staining. Lens fiber cells were removed from these mice to model cataract surgery, and the fibrotic and immune response to surgery assessed by semi-quantitative immunofluorescence testing alpha-SMA, Tenascin C, EMR1 (F4/80), CD163 and
Ki-67 expression.
Results :
Thbs1-/- mice did not exhibit notable differences in lens structure or transparency, although they had corneal opacities as previously reported. However, following lens fiber cell removal (PCS), Thbs1-/- LECs exhibited elevated levels of cell proliferation (P= 0.00005) and alpha-SMA expression (p=0.03) at 72-hours PCS compared to wildtype while tenascin C levels were similar (p=0.1). Thbs1-deficient LECs exhibit a heightened fibrotic response and a notable increase in F4/80+ macrophages infiltration at 72 hours (p=0.04), while preliminary analyses did not find statistically significant elevations in CD163+ M2 macrophages at this time point.
Conclusions :
This study reveals that the lack of Thrombospondin-1 (THBS1) in lens epithelial cells post-cataract surgery leads to heightened fibrosis and increased macrophage infiltration, highlighting THBS1's crucial role in modulating post-surgical responses.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.