Abstract
Transforming growth factor β (TGFβ)-induced epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) plays a key role in the pathogenesis of anterior subcapsular cataract (ASC) and capsule opacification. In mouse lens, Sprouty2 (Spry2) has a negative regulatory role on TGFβ signaling. However, the regulation of Spry2 during ASC development and how Spry2 modulates TGFβ signaling pathway in human LECs have not been characterized. Here, we demonstrate that Spry2 expression level is decreased in anterior capsule LECs of ASC patients. Spry2 negatively regulates TGFβ2-induced EMT and migration of LECs through inhibition of Smad2 and ERK1/2 phosphorylation. Also, blockade of Smad2 or ERK1/2 activation suppresses EMT caused by Spry2 downregulation. Collectively, our results for the first time show in human LECs that Spry2 has an inhibitory role in TGFβ signaling pathway. Our findings in human lens tissue and epithelial cells suggest that Spry2 may become a novel therapeutic target for the prevention and treatment of ASC and capsule opacification.
Highlights
Anterior subcapsular cataract (ASC) and capsule opacification are both caused by excessive proliferation and differentiation of lens epithelial cells (LECs)[1,2,3,4]
In ASC, LECs tend to transdifferentiate into myofibroblasts directly beneath the lens capsule, so a reduced expression level of Spry2 and a high level of epithelial-mesenchymal transition (EMT) could be detected in these anterior capsule samples
Cell migration was enhanced upon Spry2 downregulation and suppressed upon Spry2 overexpression (Fig 3A and 3B). These findings demonstrate that Spry2 negatively regulates TGFβ2-induced LECs migration, which is a crucial stage in the pathogenesis of Posterior capsule opacification (PCO)
Summary
Anterior subcapsular cataract (ASC) and capsule opacification are both caused by excessive proliferation and differentiation of lens epithelial cells (LECs)[1,2,3,4]. ASC is a primary cataract characterized by star-shaped or irregular fibrotic plaques beneath the anterior capsule, resulting in dramatic visual reduction due to visual axis involvement[5]. Capsule opacification is one of the most common complications after cataract surgery. Posterior capsule opacification (PCO), known as secondary cataract, results from proliferation and migration of residual lens epithelial cells across the posterior capsule. About 20%-40% adult patients develop PCO within 5 years after surgery, and the incidence is almost 100% in children[6,7,8]. Anterior capsule opacification (ACO) occurs around capsulotomy edge and usually
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