Hypertensive retinopathy in a transgenic angiotensin-based model

Author:

Reichhart Nadine1,Haase Nadine2,Crespo-Garcia Sergio1,Skosyrski Sergej1,Herrspiegel Christina1,Kociok Norbert1,Fuchshofer Rudolf3,Dillinger Andrea3,Poglitsch Marco4,Müller Dominik N.2,Joussen Antonia M.1,Luft Friedrich C.2,Dechend Ralf25,Strauß Olaf1

Affiliation:

1. Department of Ophthalmology, Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany

2. Experimental and Clinical Research Center, a joint co-operation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Lindenberger Weg 80, 13125 Berlin, Germany

3. Institute of Human Anatomy and Embryology, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany

4. Attoquant Diagnostics GmbH, Campus-Vienna-Biocenter 5, 1030 Vienna, Austria

5. HELIOS-Klinik Berlin-Buch, Schwanebecker Chaussee 50, 13125 Berlin, Germany

Abstract

Severe hypertension destroys eyesight. The RAS (renin–angiotensin system) may contribute to this. This study relied on an established angiotensin, AngII (angiotensin II)-elevated dTGR (double-transgenic rat) model and same-background SD (Sprague–Dawley) rat controls. In dTGRs, plasma levels of AngII were increased. We determined the general retinal phenotype and observed degeneration of ganglion cells that we defined as vascular degeneration. We also inspected relevant gene expression and lastly observed alterations in the outer blood–retinal barrier. We found that both scotopic a-wave and b-wave as well as oscillatory potential amplitude were significantly decreased in dTGRs, compared with SD rat controls. However, the b/a-wave ratio remained unchanged. Fluorescence angiography of the peripheral retina indicated that exudates, or fluorescein leakage, from peripheral vessels were increased in dTGRs compared with controls. Immunohistological analysis of blood vessels in retina whole-mount preparations showed structural alterations in the retina of dTGRs. We then determined the general retinal phenotype. We observed the degeneration of ganglion cells, defined vascular degenerations and finally found differential expression of RAS-related genes and angiogenic genes. We found the expression of both human angiotensinogen and human renin in the hypertensive retina. Although the renin gene expression was not altered, the AngII levels in the retina were increased 4-fold in the dTGR retina compared with that in SD rats, a finding with mechanistic implications. We suggest that alterations in the outer blood–retinal barrier could foster an area of visual-related research based on our findings. Finally, we introduce the dTGR model of retinal disease.

Publisher

Portland Press Ltd.

Subject

General Medicine

Reference74 articles.

1. Hypertensive retinopathy in severely hypertensive children: demographic, clinical, and ophthalmoscopic findings from a 30-year British cohort;Williams;J. Pediatr. Ophthalmol. Strabismus,2013

2. Grade III or grade IV hypertensive retinopathy with severely elevated blood pressure;Henderson;West. J. Emerg. Med.,2012

3. Retinal microvasculature as a model to study the manifestations of hypertension;Cheung;Hypertension,2012

4. [Ameliorative effects on retinal disorder in diabetic SHRSP (stroke-prone spontaneously hypertensive rat)];Nagisa;Nihon Rinsho,2002

5. The role of inflammation in the pathogenesis of glaucoma;Vohra;Surv. Ophthalmol.,2013

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