Mouse microphthalmia-associated transcription factor (Mitf) mutations affect the structure of the retinal vasculature.

PURPOSE:Mice carrying pathogenic variants in the microphthalmia transcription factor (Mitf) gene show structural and functional changes in the retina and retinal pigment epithelium. The purpose of this study was to assess the vascular changes in Mitf mice carrying pathogenic variants by determining their retinal vessel diameter. METHODS:Mice examined in this study were: B6-Mitfmi-vga9/+ (n = 6), B6-Mitfmi-enu22(398) /Mitfmi-enu22(398) (n = 6) and C57BL/6J wild type mice (n = 6), all 3 months old. Fundus images were taken with a Micron IV camera after intraperitoneal injection of fluorescein salt. Images were adjusted to enhance contrast and a custom written MATLAB program used to extract the mean vascular diameter at a pre-defined distance from the optic disc. The number of vessels, mean diameter and mean total diameter were examined. RESULTS:The mean diameter of retinal veins in Mitfmi-enu22(398) /Mitfmi-enu22(398) mice was 18.8% larger than in wild type (p = 0.026). No differences in the mean diameter of the retinal arteries were found between the genotypes. Mitfmi-enu22(398) /Mitfmi-enu22(398) mice have 17.2% more retinal arteries (p = 0.026), and 15.6% more retinal veins (p = 0.041) than wild type. A 24.8% increase was observed in the mean combined arterial diameter in mice with the Mitfmi-enu22(398)/ Mitfmi-enu22(398) compared to wild type mice (p = 0.024). A 38.6% increase was found in the mean combined venular diameter in mice with the Mitfmi-enu22(398) /Mitfmi-enu22(398) pathogenic variation as compared to wild type (p = 0.004). The mean combined retinal venular diameter in the Mitfmi-vga9/+ mice was 17.8% larger than in wild type (p = 0.03). CONCLUSION:An increase in vascularization of the retina in Mitfmi-enu22(398) /Mitfmi-enu22(398) mice was found, indicating an increased demand for blood flow to the retina.