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Vimentin knockdown decreases corneal opacity.
- Source :
-
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2014 May 22; Vol. 55 (7), pp. 4030-40. Date of Electronic Publication: 2014 May 22. - Publication Year :
- 2014
-
Abstract
- Purpose: 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.<br />Methods: 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.<br />Results: 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.<br />Conclusions: These findings suggest that a nonviral gene therapeutic approach has potential for treating corneal fibrosis and ultimately reducing scarring.<br /> (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)
- Subjects :
- Animals
Blotting, Western
Cells, Cultured
Cornea drug effects
Cornea metabolism
Cornea pathology
Corneal Keratocytes drug effects
Corneal Keratocytes metabolism
Corneal Keratocytes pathology
Corneal Opacity pathology
Disease Models, Animal
Eye Injuries metabolism
Eye Injuries pathology
Female
Fibrosis genetics
Fibrosis pathology
Fibrosis therapy
Follow-Up Studies
Green Fluorescent Proteins biosynthesis
Green Fluorescent Proteins genetics
Mice
Mice, Inbred C57BL
Microscopy, Confocal
Real-Time Polymerase Chain Reaction
Vimentin biosynthesis
Vimentin genetics
Wound Healing
Corneal Opacity genetics
Corneal Opacity therapy
Gene Expression Regulation
Gene Knockdown Techniques methods
RNA genetics
Vimentin therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1552-5783
- Volume :
- 55
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Investigative ophthalmology & visual science
- Publication Type :
- Academic Journal
- Accession number :
- 24854859
- Full Text :
- https://doi.org/10.1167/iovs.13-13494