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Mette Ladefoged, Christopher Mayer, Nanna Junker, Toke Bek; Identification of Retinal Vascular Markers of Early-Stage Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4923.
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Diabetic retinopathy (DR) is the leading cause of vision loss among the working age population in the Western world. The pathogenesis involves changes in metabolic parameters affecting the retinal vasculature leading to pericyte loss, endothelial dysfunction and vascular permeability. The development of new treatment modalities requires a better understanding of molecular and biochemical changes that can only be studied in animal models. The purpose of the present study was to identify early gene expression patterns that can act as markers of retinal vascular disturbances in experimentally induced diabetes in mice.
SV129 mice were induced with diabetes using streptozotocin (double intermediate dose; 125mg/kg) or vehicle (controls). After 15 weeks, animals were sacrificed and eyes enucleated and snap-frozen. Retinal vessels were isolated by hypotonic lysis. Total RNA was isolated using the RNeasy micro kit according to the manufacturer’s instructions. Differences in gene expression of selected markers were analyzed using TaqMan Array Cards containing 44 selected retinal vascular markers, including mural cell and tight junction markers.
15 weeks of streptozotocin-induced diabetes resulted in a significant change in gene expression of a number of the examined markers, including downregulation of the mural cell marker, NG-2, and the tight junction protein, ZO-1.
The results demonstrate that after 15 weeks of diabetes mellitus changes in genes coding for specific retinal vascular markers can be observed in the SV129 mouse strain. Normalization of these markers may be a potential proxy for the testing of new drugs aimed at preventing the development of diabetic retinopathy.
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