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

Department of Immunology, Monash University, Alfred Medical Research and Education Precinct (AMREP), Commercial Road, Melbourne, 3004 Victoria, Australia.
Diabetologia (Impact Factor: 6.67). 07/2011; 54(10):2724-35. DOI: 10.1007/s00125-011-2239-9
Source: PubMed


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.
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.
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.
Aliskiren provided similar or greater retinal protection than ACE inhibition and may be a potential treatment for diabetic retinopathy.

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Available from: Jennifer L Wilkinson-Berka, Sep 26, 2014
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    • "Renin inhibition counterbalanced these phenomena, whereas (P)RR blockade on top of renin inhibition did not offer additional advantages. The protective effect of aliskiren on retinal vasculopathy and inflammation in diabetic Ren2 rats is consistent with a previous report [56]. Diabetic retinopathy is not only associated with vascular dysfunction, but also with a loss of retinal neurons [57]. "
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