Reduced Ocular Blood Flow as an Early Indicator of Diabetic Retinopathy in a Mouse Model of Diabetes

Abstract

To investigate ocular blood flow and visual function in the Ins2(Akita) diabetic retinopathy mouse model at early and late time points after onset of hyperglycemia. Mice heterozygous for the Ins2(Akita) mutation, which become hyperglycemic at approximately 4 weeks old, were studied at 2.5 and 7.5 months of age, with age-matched wild-type littermates used as controls. Retinal and choroidal blood flows were noninvasively imaged at 42 × 42 × 400 μm using magnetic resonance imaging. Visual function was measured using optokinetic tracking to determine spatial frequency and contrast thresholds from the same mice. At 2.5 months, choroidal blood flow was significantly reduced (P < 0.01) by 20% in Ins2(Akita) mice (n = 13) compared with age-matched controls (n = 16), whereas retinal blood flow and visual function were not significantly affected (P > 0.05). At 7.5 months, both choroidal and retinal blood flow were significantly reduced (P < 0.05) by 27% and 28%, respectively, in Ins2(Akita) mice (n = 11) compared with age-matched controls (n = 15). Visual functions were also significantly worse (P < 0.05) in Ins2(Akita) mice at 7.5 months, as indicated by a 19% decreased spatial frequency threshold and 135% increased contrast threshold compared with age-matched controls. The magnitudes of the blood flow and vision deficits, however, were not correlated. Although both choroidal and retinal blood flow and vision were altered after prolonged diabetes in the Ins2(Akita) mouse, choroidal blood flow was reduced even in young diabetic animals, suggesting ocular blood flow deficit could be an early pathological change in diabetic retinopathy.