Longitudinal Metabolic Alterations of the Visual Cortex in Diabetic Retinopathy Rats Using High‐Field Proton Magnetic Resonance Spectroscopy

The visual impairment in diabetic retinopathy (DR) has been associated with the pathophysiological changes of the entire visual pathway. However, only a few studies have specifically examined dynamic metabolic changes in the visual cortex of DR. The purpose of the study was to longitudinally characterize dynamic metabolic alterations in the visual cortex of DR rats using 11.7 T proton magnetic resonance spectroscopy (¹H-MRS), with histopathological validation. 3-month-old male DR rats and matched healthy rats were randomly selected into the study (n = 7/group), with metabolic assessments in the visual cortex conducted at 2, 4, 6, and 8 weeks. Immunohistochemical analyses were performed at 8 weeks to evaluate visual cortex alterations. The metabolite concentration ratios were compared between DR rats and controls at different time points using repeated measures analysis of variance followed by Bonferroni post hoc tests. The comparison of immunohistochemical indicators between DR rats and controls was evaluated using independent samples t test. p < 0.05 was considered statistically significant. Compared to controls, DR rats exhibited significantly higher Ins/tCr and Cho/tCr ratios in the visual cortex at 2, 4, 6, and 8 weeks, while NAA/tCr, Glu/tCr, GABA/tCr, and Tau/tCr ratios were significantly lower, respectively (all p < 0.05). Notably, Ins/tCr and Cho/tCr progressively increased with the progression of DR, whereas NAA/tCr, Glu/tCr, GABA/tCr, and Tau/tCr gradually decreased correspondingly (all p < 0.05). At 8 weeks, DR rats showed a reduction in NeuN-, Tau-, NR2B-, and GABA_A-positive cells, along with an increased expression of GFAP-positive cells, compared to controls (all p < 0.0001). In conclusion, with the progression of DR, the dynamic metabolic alterations in the visual cortex indicated ongoing cortical degeneration, impaired neurotransmitter metabolism, dysregulated cellular homeostasis and glial cell proliferation, highlighting the underlying neurobiological mechanisms of visual impairment in DR.