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Journal of Histochemistry and Cytochemistry, Vol. 46, 1033-1042, September 1998, Copyright © 1998, The Histochemical Society, Inc.

ARTICLE

Human Corneal Epithelial Basement Membrane and Integrin Alterations in Diabetes and Diabetic Retinopathy

Alexander V. Ljubimova, Zhi-shen Huanga, Gang H. Huanga, Robert E. Burgesonb, Donald Gullbergc, Jeffrey H. Minerd, Yoshifumi Ninomiyae, Yoshikazu Sadof, and M. Cristina Kenneya
a Ophthalmology Research Laboratories, Burns & Allen Research Institute, Cedars-Sinai Medical Center, UCLA Medical School Affiliate, Los Angeles, California
b MGH/Harvard Cutaneous Biology Research Center, Massachusetts General Hospital East, Charlestown, Massachusetts
c Department of Animal Physiology, Uppsala University, Uppsala, Sweden
d Renal Division, Washington University School of Medicine, St Louis, Missouri
e Okayama University Medical School, Okayama, Japan
f Shigei Medical Research Institute, Okayama, Japan

Correspondence to: Alexander V. Ljubimov, Cedars-Sinai Medical Center, Davis-5069, 8700 Beverly Boulevard, Los Angeles, CA 90048..

Corneas of diabetic patients have abnormal healing and epithelial adhesion, which may be due to alterations of the corneal extracellular matrix (ECM) and basement membrane (BM). To identify such alterations, various ECM and BM components and integrin receptors were studied by immunofluorescence on sections of normal and diabetic human corneas. Age-matched corneas from 15 normal subjects, 10 diabetics without diabetic retinopathy (DR), and 12 diabetics with DR were used. In DR corneas, the composition of the central epithelial BM was markedly altered, compared to normal or non-DR diabetic corneas. In most cases the staining for entactin/nidogen and for chains of laminin-1 ({alpha}1ß1{gamma}1) and laminin-10 ({alpha}5ß1{gamma}1) was very weak, discontinuous, or absent over large areas. Other BM components displayed less frequent changes. The staining for {alpha}3ß1 (VLA-3) laminin binding integrin was also weak and discontinuous in DR corneal epithelium. Components of stromal ECM remained unchanged even in DR corneas. Therefore, distinct changes were identified in the composition of the epithelial BM in DR corneas. They may be due to increased degradation or decreased synthesis of BM components and related integrins. These alterations may directly contribute to the epithelial adhesion and wound healing abnormalities found in diabetic corneas. (J Histochem Cytochem 46:1033–1041, 1998)

Key Words: diabetic retinopathy, corneal epithelium, basement membrane, integrins, VLA-3, laminin chains, entactin/nidogen, type IV collagen isoforms, extracellular matrix, immunofluorescence


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