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Naseem Ansari, Min Zhang, Cheng Wang, John Papaconstantinou, Vasilis Vasiliou, Bhupendra Kaphalia; Chronic alcohol consumption and corneal pathologies: the role of aldehyde dehydrogenases. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4295.
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Chronic alcoholism has been associated with various pathologies involving oxidative damage, and may be an important and underrated risk factor for eye disease, especially since the ocular tissues are constantly exposed to oxidants. Corneal thickness and structural abnormality has been reported in chronic alcoholics, however this subject has not received due attention. Aldehyde dehydrogenases (ALDHs) play a crucial role in the detoxification of reactive and toxic lipid aldehydes, such as 4-hydroxynonenal (HNE) and thus protecting this tissue and the rest of the eye against UV-light-induced oxidative damage. We have therefore investigated the status of oxidative damage, inflammation and ALDH isozymes in corneal pathology developed in mice upon chronic alcohol consumption.
To have blood alcohol levels similar to those observed in chronic alcoholics, deer mice (deficient in hepatic alcohol dehydrogenase) were fed 3.5% ethanol via Lieber-DeCarli diet for 6 months while control mice were fed the same diet with equivalent calories replaced by maltose-dextrin. Mice were euthanized and eyes excised and fixed for morphological studies (hematoxylin and eosin staining) and immunohistochemical studies (for ALDH1A1, ALDH2, ALDH3A1, protein-acetylated lysine adducts, protein-HNE adducts, and nitric oxide synthase staining). Stained images of corneal sections were used to measure the thickness of the middle and side portions of the cornea.
Chronic ethanol treatment resulted in a dramatic increase of the corneal thickness of both the stroma and epithelial layer. Maximum change in the corneal thickness (in microns) occurred in the middle portion (Control group: stroma, 59 ±7; epithelial layer, 28 ±3 and Alcohol-treated group: stroma, 110±2; epithelial layer, 41 ± 2). Alcohol treatment led to a decrease in the expression of most of the ALDH isozymes with a concomitant increase in the oxidative and inflammatory markers and protein-acetylated lysine adducts, a potential marker of ethanol consumption.
Our results suggest that impairment in detoxification of lipid aldehydes and acetaldehyde under chronic alcohol exposure may be central to alcohol-induced changes in corneal structure and function.. Further studies using the ALDH knockout mice would lay the foundation for a novel therapeutic strategy of preserving corneal pathology in chronic alcoholics.
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