Hypertensive retinopathy in a transgenic angiotensin-based model


  • N. Reichhart
  • N. Haase
  • S. Crespo-Garcia
  • S. Skosyrski
  • C. Herrspiegel
  • N. Kociok
  • R. Fuchshofer
  • A. Dillinger
  • M. Poglitsch
  • D.N. Müller
  • A.M. Joussen
  • F.C. Luft
  • R. Dechend
  • O. Strauß


  • Clinical Science


  • Clin Sci 130 (13): 1075-1088


  • Severe hypertension destroys eyesight. The renin-angiotensin system may contribute. We relied on an established angiotensin, Ang II-elevated double-transgenic model (dTGR) and same-background Sprague-Dawley rat (SD) controls. In dTGR plasma levels of Ang II 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 expressions 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 dTGR animals, compared to SD 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 dTGR compared to controls. Immuno-histological analysis of blood vessels in retina whole-mount preparations showed structural alterations in the retina of dTGR. We then determined the general retinal phenotype. We observed the degeneration of ganglion cells, defined vascular degenerations, and finally we 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 Ang II levels in the retina were four-fold increased in the dTGR retina compared to that in SD, 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.