Hypertensive retinopathy in a transgenic angiotensin-based model

Reichhart, Nadine and Haase, Nadine and Crespo-Garcia, Sergio and Skosyrski, Sergej and Herrspiegel, Christina and Kociok, Norbert and Fuchshofer, Rudolf and Dillinger, Andrea and Poglitsch, Marco and Mueller, Dominik N. and Joussen, Antonia M. and Luft, Friedrich C. and Dechend, Ralf and Strauss, Olaf (2016) Hypertensive retinopathy in a transgenic angiotensin-based model. CLINICAL SCIENCE, 130 (13). pp. 1075-1088. ISSN 0143-5221, 1470-8736

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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.

Item Type: Article
Uncontrolled Keywords: RETINAL-PIGMENT EPITHELIUM; INTRAOCULAR-PRESSURE; OSCILLATORY POTENTIALS; DIABETIC-RETINOPATHY; OCULAR HYPERTENSION; BLOOD-PRESSURE; GROWTH-FACTOR; RAT RETINA; IN-VIVO; GLAUCOMA; blood-retina barrier; hypertensive retinopathy; renin-angiotensin system; retinal degeneration; vascular damage
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Anatomie
Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 02 Apr 2019 12:10
Last Modified: 02 Apr 2019 12:10
URI: https://pred.uni-regensburg.de/id/eprint/3643

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