Extracapsular cataract surgery is a marvel of modern medicine that has greatly reduced the global burden of cataract-related blindness. However, optimal implantation of a replacement intraocular lens requires preservation of most of the lens capsule, the basement membrane surrounding the lens. Since lens epithelial cells (LECs) are tightly attached to the lens capsule, it is not possible to remove all LECs during cataract surgery, and these cells undergo robust wound healing responses characterized by cell proliferation and the transdifferentiation of LECs to scar producing myofibroblasts. While modern intraocular lens implants can sequester myofibroblasts away from the ocular axis short term, these cells can survive long term at the periphery of the capsular bag, and often escape years after surgery, migrating into the visual axis, where they can proliferate, wrinkle the capsule, and produce fibrotic extracellular matrix molecules, leading to the onset of posterior capsular opacification (PCO) years after the initial cataract surgery. Thus, understanding the mechanisms by which myofibroblasts survive and maintain their phenotype long term is of great importance. During the last grant cycle, we discovered that fibronectin produced by lens cells after surgery was critical for the maintenance of the fibrotic phenotype of LECs post fiber cell removal. This proposal seeks to investigate the mechanisms by which fibronectin and its interacting partners mediate the fibrotic phenotype of lens epithelial cells.
Cataract surgery has greatly decreased the burden of blindness worldwide, however, current surgical methods are unable to remove all lens cells, and these undergo a wound healing response post surgery, leading to the formation of scar tissue within the eye, compromising vision. This work will provide fundamental insights into the mechanisms that lead to the inappropriate maintenance of the myofibroblasts that produce scar tissue after cataract surgery. This information will inform the design of strategies to prevent fibrotic posterior capsular opacification, yielding improved visual outcomes for cataract patients.
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