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

Stefán Broddi Daníelsson1, Andrea García-Llorca1, Hallur Reynisson1

  • 1Department of Physiology, Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavík, Iceland.

Acta Ophthalmologica
|March 29, 2022
PubMed
Abstract

Insights

Mice with pathogenic variants in the microphthalmia transcription factor (Mitf) gene exhibit increased retinal vascularization. This study quantifies these vascular changes, revealing significant increases in retinal artery and vein diameters and numbers.

Area of Science:

  • Ophthalmology
  • Genetics
  • Vascular Biology

Background:

  • Pathogenic variants in the microphthalmia transcription factor (Mitf) gene are known to cause retinal and retinal pigment epithelium abnormalities.
  • Understanding the vascular implications of Mitf gene variants is crucial for comprehending retinal development and disease.

Purpose of the Study:

  • To investigate and quantify the vascular changes in the retina of mice carrying pathogenic Mitf gene variants.
  • Specifically, to determine the retinal vessel diameter in Mitf mutant mice compared to wild-type controls.

Main Methods:

  • Three groups of 3-month-old mice were studied: B6-Mitfmi-vga9/+ (n=6), B6-Mitfmi-enu22(398) /Mitfmi-enu22(398) (n=6), and C57BL/6J wild type (n=6).
  • Fundus imaging was performed after fluorescein injection, and a custom MATLAB program was used to measure mean vascular diameters.
  • Analysis included the number of vessels, mean diameter, and mean total diameter of retinal arteries and veins.

Main Results:

  • Mitfmi-enu22(398) /Mitfmi-enu22(398) mice showed an 18.8% larger mean retinal vein diameter (p=0.026) and a 24.8% larger mean combined arterial diameter (p=0.024) compared to wild type.
  • These mice also had 17.2% more retinal arteries (p=0.026) and 15.6% more retinal veins (p=0.041).
  • A significant 38.6% increase in mean combined venular diameter (p=0.004) and a 17.8% increase in mean combined venular diameter in Mitfmi-vga9/+ mice (p=0.03) were observed.

Conclusions:

  • The study found a significant increase in retinal vascularization in Mitfmi-enu22(398) /Mitfmi-enu22(398) mice.
  • This heightened vascularization suggests an increased demand for blood flow to the retina in these Mitf mutant models.
  • These findings highlight the role of Mitf in regulating retinal vascular development.

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