Purchase this article with an account.
Changmei Guo, Peng Zhang, Zifeng Zhang, Hiroyoshi Kawada, Karen Blessing, Peter Kador; TRANSGENIC AK-SMAA-GFP-HAR MICE SUPPORT THE PREMISE THAT ALDOSE REDUCTASE INITIATES DIABETIC RETINOPATHY. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1159.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Demonstrate that AR plays a central role in the onset of diabetic retinopathy.
A colony of transgenic C57BL mice expressing green fluorescent protein (SMAA-GFP), human aldose reductase(SMAA-hAR) or both (SMAA-GFP-hAR) in vascular tissues under the control of smooth muscle alpha actin promoter have been established and crossbred with diabetic C57BL/6-Ins2Akita/J (AK) mice to produce naturally diabetic offspring of AK-SMAA-GFP or AK-SMAA-GFP-hAR. Aldose reductase inhibitors (ARIs) were administered in chow.
The presence of GFP and hAR in retinal capillary pericytes were confirmed by confocal microscopy. AK-SMAA-GFP-hAR mice had higher sorbitol and VEGF levels compared to AK-SMAA-GFP mice, which were normalized by ARI. AK-SMAA-GFP-hAR mice also showed induction of retinal growth factors IGF-1, bFGF and TGFβ, as well as signaling changes in P-Akt, P-SAPK/JNK, and P-44/42 MAPK which were normalized by ARIs. Histological evaluation of isolated retinal capillaries from 18 week old AK-SMAA-GFP-hAR mice also demonstrated increased loss of nuclei/capillary length and a significant increase in the percentage of acellular capillaries present. These changes were not observed in similar mice treated with ARI.
Diabetic mice expressing hAR in their retinal vascular tissue demonstrate capillary pathology and growth factor and signal expression associated with DR. These changes were not observed in similar mice treated with ARI, supporting the premise that AR in these transgenic mice plays a central role in DR.
This PDF is available to Subscribers Only