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.
Hypertensive retinopathy in a transgenic angiotensin-based model
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Nadine Reichhart, Nadine Haase, Sergio Crespo-Garcia, Sergej Skosyrski, Christina Herrspiegel, Norbert Kociok, Rudolf Fuchshofer, Andrea Dillinger, Marco Poglitsch, Dominik N. Müller, Antonia M. Joussen, Friedrich C. Luft, Ralf Dechend, Olaf Strauß; Hypertensive retinopathy in a transgenic angiotensin-based model. Clin Sci (Lond) 1 July 2016; 130 (13): 1075–1088. doi: https://doi.org/10.1042/CS20160092
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