Altered retinal function and eye morphology in mice with different mutations in the microphthalmia-associated transcription factor (Mitf)

Abstract

Purpose : Mutations at the mouse microphthalmia-associated transcription factor locus (Mitf) can cause hypopigmentation, microphthalmia and blindness. The aim was to analyse the retinal function and morphology of the eye in mice with four specific Mitf mutations.

Methods : The following Mitf mutations were examined: Mitf^mi-vga9/+, Mitf^{mi-enu122 (398)}, Mitf^mi-wh/+, Mitf^mi-wh/mi and wild type (C5BL/6J) mice as a control. Mice were anaesthetized by an intraperitoneal injection of 40 mg/kg^-1 Ketamine and 4 mg/kg^-1 Xylazine. Flash electroretinography (ERG) from mice with pupils dilated, a corneal electrode and a reference electrode was used to determine retinal function. Histological retinal sections were stained with hematoxylin and eosin.

Results : ERG recordings revealed that only two of the four mutants had any retinal function. Mitf^{mi-enu122 (398)} and Mitf^mi-vga9/+ had significantly larger photopic b-waves at 1.57 and 1.87 log cd*sec/m² than control (p<0.05). No differences were found between the amplitudes of the scotopic a- and b-waves of the Mitf^{mi-enu122 (398)}, Mitf^mi-vga9/+ and control. Histology revealed that the retinas in the Mitf^{mi-enu122 (398)} and Mitf^mi-vga9/+ appear normal and the RPE layer is thinner in the Mitf^{mi-enu122 (398)}, whereas Mitf^mi-vga9/+ has a pigmented choroid. However, the Mitf^mi-wh/+ have a profound RPE degeneration and this layer is missing from the Mitf^mi-wh/mi animals. Both mutations have severe retinal degeneration, lacking the photoreceptor and outer plexiform layers, and extinguished ERGs.

Conclusions : This study demonstrates that the Mitf gene has an impact on retinal function, the morphology of the neuroretina and the RPE in mice to a varying degree, depending on the mutations involved.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.