Retinal function and morphology in Mitf mutant mice

Purpose The Mitf (microphthalmia‐associated transcription factor) gene that is essential for the normal development of the retinal pigment epithelium (RPE). Mutations in this gene can cause hypopigmentation, microphthalmia and blindness. The purpose of this work was to analyze the retinal function and morphology in mice with specific Mitf mutations. Methods The following Mitf mutations were used: Mitfmi‐enu122 (398), Mitfmi‐wh/+, Mitfmi‐wh/Mitfmi and wild type (C5BL/6J) mice as a control. Mice were anesthetized by an intraperitoneal injection of 40 mg/kg −1 Ketamine and 4 mg/kg −1 Xylazine. Flash electroretinography (ERG), from mice with pupils dilated, with a corneal electrode and a reference electrode placed in the mouth, was used to determine the role of the MITF protein in retinal function. Histological retinal sections were stained with hematoxylin and eosin. Results ERG recordings revealed that only one of the four mutants had any retinal function. The wild type mice had significantly higher mean amplitudes of the photopic a‐waves and scotopic oscillatory potentials than the Mitfmi‐enu122 (398) animals ( α = 0.05). Furthermore, Mitfmi‐enu122 (398) had significantly shorter implicit times for the photopic b‐waves and c‐waves. Histology revealed that the RPE layer in the Mitfmi‐enu122 (398) and shows localized thinning of the RPE and their retinas look normal. However, the Mitfmi‐wh/+ showed a profound RPE degeneration and this layer is missing from the Mitfmi‐wh/Mitfmi animals. Furthermore, Mitfmi‐wh/+ and Mitfmi‐wh/Mitfmi have an immense retinal degeneration, lacking the photoreceptor and outer plexiform layers. Conclusions This study demonstrates that the Mitf gene has an impact on retinal function in mice, and the morphology of the neuroretina and the RPE.