title: Hypertensive retinopathy in a transgenic angiotensin-based model.
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.
authors.affiliation: Department of Ophthalmology, Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Reichhart
authors.affiliation: 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.
authors.forename: Nadine
authors.initials: N
authors.lastname: Haase
authors.affiliation: Department of Ophthalmology, Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Sergio
authors.initials: S
authors.lastname: Crespo-Garcia
authors.affiliation: Department of Ophthalmology, Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Sergej
authors.initials: S
authors.lastname: Skosyrski
authors.affiliation: Department of Ophthalmology, Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Herrspiegel
authors.affiliation: Department of Ophthalmology, Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Kociok
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Fuchshofer
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dillinger
authors.affiliation: Attoquant Diagnostics GmbH, Campus-Vienna-Biocenter 5, 1030 Vienna, Austria.
authors.forename: Marco
authors.initials: M
authors.lastname: Poglitsch
authors.affiliation: 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.
authors.forename: Dominik N
authors.initials: DN
authors.lastname: Müller
authors.affiliation: Department of Ophthalmology, Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Antonia M
authors.initials: AM
authors.lastname: Joussen
authors.affiliation: 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.
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.affiliation: 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 HELIOS-Klinik Berlin-Buch, Schwanebecker Chaussee 50, 13125 Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.affiliation: Department of Ophthalmology, Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany olaf.strauss@charite.de.
authors.forename: Olaf
authors.initials: O
authors.lastname: Strauß
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D058437:Hypertensive Retinopathy / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D055647:Rats, Transgenic; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics*
chemical_list: D000808:Angiotensinogen; D000804:Angiotensin II; D012083:Renin
keywords: blood–retina barrier; hypertensive retinopathy; renin–angiotensin system; retinal degeneration; vascular damage