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Diabetologia
Published in: Diabetologia 10/2011

01-10-2011 | Article

Aliskiren reduces vascular pathology in diabetic retinopathy and oxygen-induced retinopathy in the transgenic (mRen-2)27 rat

Authors: J. L. Wilkinson-Berka, G. Tan, K. J. Binger, L. Sutton, K. McMaster, D. Deliyanti, G. Perera, D. J. Campbell, A. G. Miller

Published in: Diabetologia | Issue 10/2011

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Abstract

Aim/hypothesis

We examined whether the renin inhibitor, aliskiren, provides similar or greater protection than ACE inhibition from non-proliferative diabetic retinopathy and from the proliferative neoangiogenesis of oxygen-induced retinopathy.

Methods

Transgenic (mRen-2)27 rats, which overexpress mouse renin and angiotensin in extra-renal tissues, were studied. For diabetic studies, non-diabetic, diabetic (streptozotocin, 55 mg/kg), diabetic + aliskiren (10 mg kg−1 day−1, pump), or diabetic + lisinopril (10 mg kg−1 day−1, drinking water) rats were evaluated over 16 weeks. For oxygen-induced retinopathy studies, rats were exposed to 80% oxygen (22 h/day) from postnatal days 0 to 11, and then room air from postnatal days 12 to 18. Aliskiren (10 or 30 mg kg−1 day−1, pump) or lisinopril (10 mg kg−1 day−1, drinking water) was administered during retinopathy development between postnatal days 12 and 18.

Results

Systolic BP in diabetic (mRen-2)27 rats was reduced with 10 mg kg−1 day−1 aliskiren, but only lisinopril normalised systolic blood pressure. In diabetic (mRen-2)27 rats, 10 mg kg−1 day−1 aliskiren and lisinopril reduced retinal acellular capillaries and leucostasis to non-diabetic levels. In oxygen-induced retinopathy, neoangiogenesis and retinal inflammation (leucostasis, ED-1 immunolabelling) were partially reduced by 10 mg kg−1 day−1 aliskiren and normalised by 30 mg kg−1 day−1 aliskiren, whereas lisinopril normalised neoangiogenesis and reduced leucostasis and ED-1 immunolabelling. Aliskiren and lisinopril normalised retinal vascular endothelial growth factor expression; however, only aliskiren reduced intercellular adhesion molecule-1 to control levels.

Conclusions/interpretation

Aliskiren provided similar or greater retinal protection than ACE inhibition and may be a potential treatment for diabetic retinopathy.
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Metadata
Title
Aliskiren reduces vascular pathology in diabetic retinopathy and oxygen-induced retinopathy in the transgenic (mRen-2)27 rat
Authors
J. L. Wilkinson-Berka
G. Tan
K. J. Binger
L. Sutton
K. McMaster
D. Deliyanti
G. Perera
D. J. Campbell
A. G. Miller
Publication date
01-10-2011
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 10/2011
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-011-2239-9

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