Abstract
Purpose :
This study validates the use of the C57BL/6JBomTac mouse model as a potential control in studies that investigate diabetic retinopathy (DR). C57BL/6J (B6J) mouse strain has been used as an inbred control in diabetes mellitus (DM) and DR studies. However, B6J mice display impaired glucose intolerance and reduced insulin secretion due to a spontaneous mutation in the nicotinamide nucleotide transhydrogenase (Nnt). It’s been reported that Nnt mutation enhances glucose-dependent ROS production, increases oxidative damage and impairs β-cell mitochondrial metabolism. Ample evidence indicates that mitochondrial dysfunction plays a major role in developing DM with the accompanying risk for developing DR. Arguably, using B6J mice in studies that focus on mitochondrial dysfunctional diseases, such as DM and DR, would be especially concerning, given the direct effect of Nnt’s loss of function on the mitochondrial NADP status and the overall redox balance. Against such a genetic background, the development of DM and DR is likely going to occur. It is therefore prudent to explore the use of other animal models that don’t display the Nnt mutation, DM or DR.
Methods :
We examined 14 intervals throughout the growth of the C57BL/6JBomTac mouse that doesn’t carry the Nnt mutation, using fluorescein angiography (FA), optical coherence tomography (OCT), electroretinography (ERG) and trypsin digestion (TD) studies.
Results :
FA revealed that all mice exhibited healthy retinas characterized by dense capillary network, normal retinal blood vessels and vasculature that exhibited the absence of vascular leakages or hemorrhages. OCT scans exhibited normal comparable thickness of healthy retinal layers throughout the areas of section scans. ERG revealed that visual responsiveness was characterized by a- and b-waves that remained normal in waveform and amplitude. TD sections displayed healthy vasculature that presented vigorous retinal angiogenesis and normal endothelial to pericyte ratios, while ghost perciytes and acellular capillaries were absent.
Conclusions :
This report identifies the C57BL/6JBomTac mouse model as a potential control in DM and DR studies. Our study offers a word of caution concerning the use of Nnt-mutated B6J mouse as a model to investigate diseases that are pertinent to metabolism or mitochondrial pathophysiology.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.