Arginase-1 promotes lens epithelial-to-mesenchymal transition in different models of anterior subcapsular cataract

Arginase-1 (ARG1) promotes collagen synthesis and cell proliferation. ARG1 is highly expressed in various tumour cells. The mechanisms of ARG1 in epithelial-to-mesenchymal transition (EMT)-associated cataracts were studied herein. C57BL/6 mice, a human lens epithelial cell line (HLEC-SRA01/04), and human lens capsule samples were used in this study. The right lens anterior capsule of the mouse eye was punctured through the central cornea with a 26-gauge hypodermic needle. Human lens epithelial cells (HLECs) were transfected with ARG1-targeted (siARG1) or negative control siRNA (siNC). For gene overexpression, HLECs were transfected with a plasmid bearing the ARG1 coding sequence or an empty vector. Medium containing 0.2 Fibrotic cataracts can be classified as anterior subcapsular cataract or posterior capsular opacification depending on where fibrosis occurs. The mechanism of fibrotic cataracts is not fully understood. Fibrotic opacities induced by trauma, inflammation, or radiation can accumulate underneath the anterior lens capsule, causing anterior subcapsular cataract. Posterior capsular opacification is one of the most common complications of phacoemulsification with intraocular lens implantation, with a high incidence in young patients. We show for the first time that ARG1 can regulate EMT in fibrotic cataracts. TGF-β2 is the main cause of fibrosis in LECs. The expression of ARG1 and fibronectin in LECs increased after TGF-β2 treatment or mouse lens capsular injury. We investigated the specific molecular mechanisms by which ARG1 regulates EMT in fibrotic cataracts. The mRNA expression of enzymes of the arginase-related pathway was decreased due to knockdown of ARG1 expression in HLECs. These effects were reversed by ARG1 overexpression. Additionally, knockdown of ARG1 decreased collagen 1A1, fibronectin, and vimentin expression; superoxide levels; and cell migration and increased NO levels. These effects were reversed by ARG1 overexpression. Pharmacological blockade of the ARG1 pathway with CB-1158 reduced the proliferation of LECs and decreased fibronectin, α-SMA, collagen 1A1, and vimentin expression in mouse lenses. We believe that ARG1 promotes the production of collagen 1A1 by directly activating the arginase pathway and leads to lens fibrosis by reducing NO production and increasing superoxide levels, providing a new mechanism for the prevention and treatment of fibrotic cataracts.