Correlation analysis between early visual function impairment and neuron function abnormality in diabetic mouse primary visual cortex

Objective

To investigate the damage of visual function in the early stage of diabetes mellitus and the response characteristics of primary visual cortex neurons in diabetic mice.

Methods

Twenty 7-week-old SPF grade male C57BL/6J mice were randomly divided into diabetes group and normal control group by the random number table method, with 10 mice in each group.The diabetes model in diabetes group was established by the intraperitoneal injection of streptozotocin.Fasting blood glucose concentration and body mass of mice were measured before and 1, 2 and 3 weeks after modeling, and intraperitoneal glucose tolerance test was performed 4 weeks after modeling to evaluate the establishment of diabetes model.At 4 weeks after modeling, the electroretinogram (ERG) responses of mice were recorded at dark adaptation luminances of 0.01 and 3.0 cd·s/m², and the ERG response to light adaptation luminance of 3.0 cd·s/m² was recorded 10 minutes after light adaptation to evaluate the retinal function of mice.The fundus of mice was examined with an ultra-wide field laser scanning ophthalmoscope.The visual function of mice was evaluated via the cutoff frequency of grating discrimination detected by visual water maze.The spatial frequency tuning curves of primary visual cortex (V1) neurons were detected by in vivo electrophysiology technique and the maximum firing intensity, self-firing intensity, optimal spatial frequency, cutoff frequency and bandwidth of neurons were calculated to evaluate the neuronal function of mice.The research scheme was approved by the Experimental Animal Ethics Committee of Anhui Medical University (No.LLSC20230419).

Results

The diabetic model was successfully established in 10 mice in the diabetes group.At 4 weeks after modeling, compared with the normal control group, the b-wave amplitudes of mice at a dark adaptation luminance of 0.01 cd·s/m², the a- and b-wave amplitudes of mice at a dark adaptation luminance of 3.0 cd·s/m² and the b-wave amplitudes of mice at a light adaptation luminance of 3.0 cd·s/m² after 10 minutes of light adaptation showed a downward trend in diabetes group, but the differences were not statistically significant (all at P>0.05).Ultra-wide field laser scanning ophthalmoscopy showed no obvious vascular changes in the retina of diabetic mice.The results of visual water maze detection showed that the cutoff frequency of diabetes group was (0.45±0.06)c/d, which was significantly lower than (0.58±0.05)c/d of normal control group (t=5.10, P<0.05).In vivo electrophysiological results showed that the maximum firing intensity of neurons in V1 region in diabetes group 4.29(2.60, 8.33)spikes/second, which was significantly lower than 7.10(4.34, 11.6)spikes/second in normal control group(Z=-4.29, P<0.05).The optimal spatial frequency, cutoff spatial frequency and bandwidth were 0.03(0.02, 0.05), 0.07(0.05, 0.12) and 0.14(0.07, 0.22)c/d in diabetes group, which were significantly lower than 0.41(0.03, 0.05) and 0.10(0.07, 0.14), 0.14(0.10, 0.26)c/d of normal control group, and the differences were statistically significant (Z=-3.22, -3.19, -2.19; all at P<0.05).

Conclusions

The abnormal visual function may occur in the early stage of diabetes before the appearance of retinal vasculopathy, which is related to the damage of neurons in the V1 region.

Diabetes mellitus; Retina; Primary visual cortex; Visual water maze; Electroretinogram; Electrophysiology; Mice