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Provost Alexandra, Brahim El Mathari, Alexandra Trehin, Carine Bernard, Damien Lavier, Annabelle Amiard, Manuel SIMONUTTI, Anais Potey, Samantha Beck, Thomas Debeir; 3 months kinetics of Type 1 Diabetes model in Brown Norway rats : Retinal phenotypes and molecular analysis. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5182.
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Diabetes is associated with retinal microvascular changes that include leakage and leukostatis, leading to diabetic retinopathy. We investigated the Brown Norway rat during a 3 month period, after induction of diabetes by streptozotocin (STZ), to determine if this pigmented strain develops early-stage diabetic retinopathy.
Diabetes was induced in Brown Norway rats with a single IP injection of streptozotocin (65mg/kg). Diabetic and non-diabetic animals were examined over a period of 3 months to monitor changes in retinal vascular pathology using in vivo fluorescein angiography, functional alterations using electroretinography (ERG), and modifications in blood-retinal barrier permeability using blue Evans perfusion. Further, loss of pericytes and acellular capillaries was caracterized by periodic acid shiff staining (PAS), Adhesion of leukocytes at the retinal vessels was assessed by concanavaline A staining, and neuro-inflammation was explored by Quantitative PCR and immunohistochemistry of retinal sections.
3 months after induction of diabetes in the Brown Norway rats, the PAS and retinal permeability analysis showed no evidence of vascular and morphological changes such as degenerated capillaries and pericytes ghosts. Fluorescein angiography was difficult to analyse because of diabetes induced lens opacification. However, at ERG, there was impairment of dark-adapted a and b-wave latency, but without modification of dark-adapted a and b-wave amplitude, in the diabetic rats. Further, inflammatory markers such as GFAP and IBA1 were more expressed on retinal sections under diabetic conditions versus controls, especially in the ganglionic cell layer. Finally, molecular analysis showed an increased expression of inflammatory genes in the retina of diabetic rats (GFAP, CXCL9-10-11), and the retinal leukostasis assay demonstrated an increase of leukocyte adherence to the retinal vasculature as compared to controls.
Over the 3 month period following induction of diabetes, the Brown Norway rats did not present with a diabetic retinopathy characterized by degeneration of retinal capillaries but showed early neuro-inflammation and alteration of visual function.
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