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H. Uehara, J. Cahoon, S. Oblad, J. Simonis, L. Luo, B. K. Ambati; Noncnzo10/ltj Mouse, a Model of Type 2 Diabetes, May Not Be Suitable for Diabetic Retinopathy Study. Invest. Ophthalmol. Vis. Sci. 2010;51(13):118.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy is one complication of diabetes mellitus. Many rodent models of diabetes have been used to understand the mechanism of, and improve, diabetic retinopathy. In this study, we characterized retina of NONcNZO10/Ltj males, which was recently generated as a mouse model of Type 2 diabetes mellitus.
NONcNZO10/Ltj males were obtained from Jackson laboratory and fed with a high fat diet. To observe retina vascularity in vivo, fluorescein angiography was used. Retina flatmounts were stained with isolectin GS-IB4 for vessel endothelial cells and α-SMA for pericytes. They were then observed with confocal microscopy. To determine retina thickness and examine retina layer composition, we used optical coherence tomography (OCT) and cryosection. In addition, we examined expression of PDE6α, PDE6β, and PDE6γ in the retina by RT-PCR and checked rd1 mutation by genotyping.
Fluorescein angiography and retina flat mount analysis showed that NONcNZO10/Ltj retina has less vasculature compared with control mouse, but pericytes still exist with retina blood vessels. In addition, high backgrounds were observed in NONcNZO10/Ltj mouse by fluorescein angiography. Retina thickness of NONcNZO10/Ltj was dramatically thinner than control mouse. OCT showed the thickness of NONcNZO10/Ltj and control retina as 137±13µm and 281±25 µm respectively. Cryosection of NONcNZO10/Ltj eye also showed thin retina (NONcNZO10/Ltj retina: 93±12µm; Control retina: 203±18µm). Nuclear observation indicated that the outer nuclear layer of NONcNZO10/Ltj was atrophic. From RT-PCR, PDE6α and PDE6β did not express in NONcNZO10/Ltj retina, but PDE6γ was still expressed. Genotyping for rd1 indicated NONcNZO10/Ltj is a rd1/rd1 mouse.
From these results, we confirmed NONcNZO10/Ltj mouse retina degeneration comes from rd1 mutation. Although fluorescein angiography indicated NONcNZO10/Ltj retina has leakage, which is a manifestation of diabetic retinopathy, NONcNZO10/Ltj mouse may not be suitable for diabetic retinopathy studies because the outer nuclear layer progressively atrophies.
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