Fibrosis: Shared Lessons From the Lens and Cornea

Abstract

Regenerative repair in response to wounding involves cell proliferation and migration. This is followed by the reestablishment of cell structure and organization and a dynamic process of remodeling and restoration of the injured cells' extracellular matrix microenvironment and the integration of the newly synthesized matrix into the surrounding tissue. Fibrosis in the lungs, liver, and heart can lead to loss of life and in the eye to loss of vision. Learning to control fibrosis and restore normal tissue function after injury repair remains a goal of research in this area. Here we use knowledge gained using the lens and the cornea to provide insight into how fibrosis develops and clues to how it can be controlled. The lens and cornea are less complex than other tissues that develop life-threatening fibrosis, but they are well characterized and research using them as model systems to study fibrosis is leading toward an improved understanding of fibrosis. Here we summarize the current state of the literature and how it is leading to promising new treatments.

Immune responses to injury and their links to eye disease

“…The de novo synthesis of collagen, elastin, and proteoglycans in the cornea stroma is mediated by smooth muscle actin+ (SMA+) myofibroblasts. Myofibroblasts differentiate from both corneal stromal keratocytes and fibrocytes during the response to ocular trauma [43][44][45]. Fibrocytes differentiate from recruited monocytes and/or resident tissue macrophages.…”

Long-Term Safety and Tolerability of BMP7 and HGF Gene Overexpression in Rabbit Cornea

“…Fibrosis after corneal injury is a common cause of visual disability that affects millions of patients worldwide. [1][2][3][4][5][6] The pathogenesis of corneal fibrosis is a complex cascade of molecular signaling events involving numerous cytokines, growth factors, and ECM remodeling factors. Currently, pharmacologic therapies are commonly used to treat corneal fibrosis despite limitations in efficacy, safety, and tolerability.…”

“…[1][2][3] Several co-morbidities are associated with corneal fibrosis, including inflammation, neovascularization, and elevated intraocular pressure. [4][5][6] Although decades of research regarding fibrosis have helped elucidate the underlying mechanisms, safe and tolerable nonsurgical treatments are currently limited. According to the National Center for Advancing Translational Sciences, only 500 human diseases are treatable with an estimated 10,000 drugs available to date, which underscores the necessity to develop new drugs and treatment options.…”

Safety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin C in reducing pro-fibrotic changes in human corneal epithelial cells

“…Usage of MMC in ophthalmic surgery was first done as an adjunct in pterygium excision in 1963 and it first use as a corneal healing modulator was performed after almost after more than 35 years in PRK 29 , 30 . MMC prevents sub-epithelial haze by inducing senescence in activated keratocytes thereby reducing the abnormal ECM by attenuating the TGFβ1 signalling in activated fibroblasts 8 , 31 . Epithelial basement membrane proteins such as laminin332, perlecan, nidogen are enhanced by MMC treated corneal epithelial cells 9 , 32 .…”