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Sonny Caplash, Paola Bargagna-Mohan, Alexandra Pietraszkiewicz, Christopher Hampton, Royce Mohan; Differential Corneal Fibrosis in Desmin Deficiency. Invest. Ophthalmol. Vis. Sci. 2017;58(8):148.
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© ARVO (1962-2015); The Authors (2016-present)
Homozygous desmin-deficient mice exhibit restrictive cardiomyopathy showing extensive fibrosis of the myocardium and reduced cardiac output by the age of 1 year (Int J Cardiovasc Imaging. 2012, 28:1699-705). We investigated the corneal phenotype in desmin deficiency in older mice and also the injury response in younger adults to differing levels of alkali injury.
The corneal alkali injury model was employed using equal numbers of male and female wild type (WT), heterozygous Des+/-, and homozygous Des-/- mice aged 2-4 months. A mild injury (1μl of 0.15N NaOH/1 minute application; N=8/genotype) or severe injury (1μl of 1N NaOH/45 seconds application; N=8/genotype) was performed. Mouse eyes were rinsed with sterile buffered saline and corneal epithelium was gently removed. Mice recovered for 7 days following severe injury and 14 days following mild injury. Corneal transparency was assessed via biomicroscopy, and for mild injury, corneal digital images were coded and graded in a blinded manner by 3 reviewers. Tissue sections from the cornea were stained with DAPI, and for immunohistochemistry (IHC), antibodies against α-SMA, Ser38 phosphorylated vimentin (pSer38 vim) and vimentin were employed.
WT, Des+/- and Des-/- mice aged to 1 year showed no loss in corneal transparency (p<0.001), corroborated by an absence of corneal stromal staining for α-SMA. pSer38vim and vimentin expression also showed no differences as compared to that in younger mice by IHC. All three older uninjured cohorts showed no sex-related differences in corneal transparency. We found increased fibrosis in WT and Des-/- mice to mild injury (p<0.001), but no sex related differences. However, injured Des+/- mice exhibited corneal haze (p<0.001) with reduced pSer38vim expression. Des+/- mice showed no sex-related differences in corneal haze. After severe injury, Des+/- mice showed similar high levels of corneal opacity as Des-/- and WT mice (p<0.05). A pilot analysis of the severe injury cohorts showed a central acellular region in corneas from all 3 genotypes. This region varied in size, with Des-/- mice having a larger region of acellularity than Des+/- mice.
A corneal phenotype was not revealed in desmin deficiency in the uninjured state. Protection from fibrosis in Des+/- mice is lost upon severe alkali injury, suggesting that desmin has both a beneficial and detrimental role in corneal wound healing that may be context related.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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