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Nadine Reichhart, Sergio Crespo-Garcia, Nadine Haase, Christina Herrspiegel, Sergej Skosyrski, Norbert Kociok, Ralf Dechend, Antonia Joussen, Olaf Strauss; dTGR: A new rat model for systemic hypertensive retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5429.
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To understand the pathomechanisms underlying hypertensive retinopathy as an example of end-organ damage, we used a double transgenic rat model (dTGR), which expresses both the rat and human renin-angiotensin system (RAS). This model leads to severe end-organ damage with animals dying by week 7 due to hypertension and high ANGII levels. Since hypertension is an important risk factor for neuronal damage in glaucoma and diabetic retinopathy, purpose of the study is to assess whether systemic hypertension affects retinal structure and function.
All experiments were performed using 7 week old dTGR and age matched Sprague-Dawley (SD) control animals. Retinal structure was assessed by immunohistochemistry and its function by GanzfeldERG and PatternERG (PERG). Fluorescein angiography (FAG) and flatmount preparations of the retina provided information about the vascular status both in vivo and ex vivo. Differential gene expression was assessed by taqmanPCR.
In HE stainings on one hand and Pattern ERG on the other hand, we were able to show both a structural and functional loss of ganglion cells in the retina of dTGR. Ganzfeld ERG revealed a mild loss of photoreceptor function. By GFAP stainings of sagittal sections of the retina and the optic nerve, we were able to detect an activation of both astrocytes and Müller cells and an astrocytosis of the optic nerve in dTGR.<br /> Flatmount preparations of the retina revealed pathological vessels with irregularities in shape and diameter compared to control animals, losing their pericyte coating. FAG showed vascular leakage and hypoxic areas in the choroid. An upregulation of VEGF-A in the GCL and INL was observed in sagittal sections, whereas the gene expression of FLT-1, sFlt-1 and Flk-1 remained unchanged. There was no differential regulation in RAS related genes in dTGR except a downregulation of the ATR1.<br /> Both staining of RPE flatmounts and qPCR showed a downregulation of claudin-1 and occludin-1 whereas the ZO-1 expression in the RPE remained unchanged.
Thus we present an animal model for hypertensive retinopathy showing functional and structural alterations of the retina. In this model, loss of barrier function of the RPE could be the cause for photoreceptor degeneration and blood vessel alteration in the retinal periphery the cause for ganglion cell loss.
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