Abstract
Purpose Secondary open-angle glaucoma may develop as a postoperative complication of early childhood cataract surgery. Its mechanism is poorly understood. Surgical removal of cataracts is typically incomplete, and we estimate that this disease is associated with alpha-B crystallin (CRYAB) secreted from the retained lens material. This study, for the first time, focused on the role of CRYAB in undesired changes of the structures and functions in trabecular meshwork (TM) cells. Methods Cell proliferation and migration were assessed using a cell counting kit-8 (CCK8) and transwell assay analysis, respectively. Immunofluorescence (IF), quantitative real-time PCR (Rt-qPCR), and Western blot were performed to determine the effect of CRYAB on F-actin, tight junctions, and the expression of epithelial to mesenchymal transition- (EMT-) associated proteins in TM cells. Results CRYAB promoted proliferation (p < 0.0001), migration (p < 0.001), and F-actin reorganization in TM cells. There were statistically significant increases in the mRNA and protein levels of zo-1, cadherin-N, and vimentin (all p < 0.0001) and cadherin-E decreased (p < 0.0001) and the mRNA level of claudin-1 increased (p < 0.0001) compared to those of the control group. Conclusion All of the changes in structures and functions first observed in the TM cells after exposure to CRYAB resembled alterations seen in primary open-angle glaucoma, suggesting that CRYAB might be related to the pathogenesis of secondary open-angle glaucoma after congenital cataract surgery.
Highlights
Cataracts are a major cause of visual disability in childhood
One study points out that the volume of trabecular cells (TM) increases as well the expression of genes and proteins related to cell morphological characteristics, inflammatory response, and ion balance regulation after trabecular meshwork (TM) are cocultured with lens epithelial cells (LECs), which is similar to the change in TM in primary open-angle glaucoma [12]
We reported that CRYAB promoted the proliferation and migration of TM cells
Summary
Cataracts are a major cause of visual disability in childhood. For children with a significant disorder of visual acuity in infancy, early congenital cataract extraction combined with posterior capsule resection and preoperative vitrectomy is conducive for restoring vision and reducing amblyopia and blindness. In the first year after birth, lensectomy increases the incidence of postoperative secondary openangle glaucoma [1,2,3], a slightly threatening complication with an incidence ranging from 6% to 58.7%, according to the variable population definition and follow-up time [4,5,6,7,8,9] Once it occurs, treatment is difficult and prognosis is poor. CRYAB likely causes the above changes in trabecular extracellular matrix and promotes epithelial to interstitial transformation, leading to the incidence of postoperative glaucoma This prompted us to undertake this study, for the first time, to investigate whether CRYAB secreted from the retained lens material negatively affects the TM cellular structures and functions by EMT and its relation with the pathogenesis of secondary openangle glaucoma
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