Human Corneal Epithelial Basement Membrane and Integrin Alterations in Diabetes and Diabetic Retinopathy¹

Abstract

SUMMARYCorneas 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 ( ␣1 ␤1 ␥1) and laminin-10 ( ␣5 ␤1 ␥1) was very weak, discontinuous, or absent over large areas. Other BM components displayed less frequent changes. The staining for ␣3 ␤1 (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)

Substance P Promotes Diabetic Corneal Epithelial Wound Healing Through Molecular Mechanisms Mediated via the Neurokinin-1 Receptor

“…The uncontrolled impairment of corneal wound healing increases the susceptibility of corneal ulcer, microbial keratitis, and even perforation. Diabetic corneal pathology always exhibits epithelial basement membrane abnormalities, reduced hemidesmosome density, and delayed wound healing (3,4). However, hyperglycemia also directly impairs the cellular metabolism and causes abnormal changes of corneal epithelium, such as Akt-, epidermal growth factor receptor (EGFR)-, and Sirt1-mediated cell responses to environmental challenges (5)(6)(7).…”

Optical quality of the diabetic eye: a review

“…30 Some studies with fluorophotometry show that this barrier function is weakened in DM leading to an increase in permeability to fluorescein. 30,31 The corneal epithelium in patients with DM exhibits alterations in both cellular components and basal membrane, which could impair the physiology of the corneal epithelial barrier function 32 and cause the cornea to be more vulnerable to foreign pathogens, such as bacteria and fungi.…”

“…32 Although the cause of theses abnormalities is not clear, some studies suggested that these disorders may be due to altered basal membrane structure and/or epithelial integrin expression, 28,31 increased glycosylation of type IV collagen 32 and fibronectin, abnormal regulation of the synthesis of extracellular matrix, increased IV collagen, and decreased laminin 31 and heparin sulfate. 27 As far as epithelial basal membrane alteration is concerned, people with DM show an accumulation of fibrillar and granular material between the epithelial cells and Bowman's membrane, thickening and multilayering of the basal membrane, 32,33 and accumulation of glycation end products (AGEs).…”

“…27,28,31 With regards to corneal stroma, Rehany et al 32 observed that stromal keratocytes contain vacuoles of lipids and prominent endoplasmic reticulum, and in DM both stroma and Descemet's membrane are loaded with randomly distributed aggregates of normally spaced collagen fibrils. Also, wrinkles in Descemet's membrane may occur and may be considered as a sign of increased corneal hydration.…”

“…89 As previously discussed, the cornea undergoes changes associated with DM, such as corneal oedema, 36 increased corneal thickness, 37,38 and abnormalities of basement membrane. 31,32 These changes could lead to an increase of light scattering as it passes through it, due to local fluctuations in refractive indices of the oedematous cornea, increased hydration, or disruption of the orientation of the collagen fibres. Morishige et al 90 measured the scattering of the corneal epithelial basement membrane in 65 patients with type 2 DM with DR and 18 healthy subjects and found that the light scattering index (LSI) was significantly higher in people with DM with PDR compared with healthy subjects.…”