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Subrata K. Das, Isha Gupta, Yang Kyung Cho, Xiaohui Zhang, Hironori Uehara, Santosh Kumar Muddana, Ashlie A. Bernhisel, Bonnie Archer, Balamurali K. Ambati; Vimentin Knockdown Decreases Corneal Opacity. Invest. Ophthalmol. Vis. Sci. 2014;55(7):4030-4040. doi: 10.1167/iovs.13-13494.
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Wound induced corneal fibrosis can lead to permanent visual impairment. Keratocyte activation and differentiation play a key role in fibrosis, and vimentin, a major structural type III intermediate filament, is a required component of this process. The purpose of our study was to develop a nonviral therapeutic strategy for treating corneal fibrosis in which we targeted the knockdown of vimentin.
To determine the duration of plasmid expression in corneal keratocytes, we injected a naked plasmid expressing green fluorescent protein (GFP; pCMV-GFP) into an unwounded mouse corneal stroma. We then injected pCMV-GFP or plasmids expressing small hairpin RNA in the corneal wound injury model (full-thickness corneal incision) to evaluate opacification.
GFP expression peaked between days 1 and 3 and had prominent expression for 15 days. In the corneal wound injury model, we found that the GFP-positive cells demonstrated extensive dendritic-like processes that extended to adjacent cells, whereas the vimentin knockdown model showed significantly reduced corneal opacity.
These findings suggest that a nonviral gene therapeutic approach has potential for treating corneal fibrosis and ultimately reducing scarring.
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