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Laura Kowalczuk, Gaël Latour, Jean-Louis Bourges, Michèle Savoldelli, Jean-Claude Jeanny, Marie-Claire Schanne-Klein, Francine Behar-Cohen; Hyperglycemia-induced corneal abnormalities in diabetic rats and humans. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3585.
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Diabetic retinopathy is detected at the earliest by retinal microangiopathy. However, alterations of retinal functions have been shown to precede the first clinical signs of retinopathy. This study aims to highlight corneal structural abnormalities induced by diabetes to provide earlier diagnosis of hyperglycemia-induced changes in the eye.
Corneas from age-matched control and Goto-Kakizaki rats, a spontaneous model of type 2 diabetes, and corneas from human donors with type 2-diabetes and without any diabetes, were included in the study. After in vivo corneal confocal microscopy examination, histology and Second Harmonic Generation (SHG) microscopy were used to characterize the ultra-structure and the three-dimensional organization of the abnormalities.
In Goto-Kakizaki rats, confocal microscopy and histology highlighted structural changes in all the layers, mainly: structural abnormalities at the epithelium-stroma interface and deposits of long-spacing fibrillar collagen in the Descemet's membrane. As these deposits appeared as soon as the diabetes beginning in this model of diabetes mellitus, we focus our attention on the easiest way to specifically detect them using SHG microscopy. In rat and human diabetic corneas, it provided background-free SHG images of the three-dimensional interwoven distribution of the collagen deposits in the Descemet’s membrane, with much improved contrast than in confocal microscopy. It also provided structural capability in intact corneas because of its high specificity to fibrillar collagen, with much larger field of view than transmission electron microscopy.
Our observations in the Descemet’s membrane demonstrate that diabetes alters the collagen structure of this layer, with the formation of long-spacing collagen fibrils synthesized by endothelium cells. Whether these changes could be correlated to blood sugar level control remains to be demonstrated. Moreover, we have shown that SHG microscopy, an emerging multiphoton imaging method that is highly specific for collagen fibrils, could provide a diagnosis for chronic hyperglycemia-induced effects in the corneal tissue. Further studies are required to evaluate if diabetes-induced corneal collagen alterations can predict the development of diabetic retinopathy.
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