RPE mutations lead to retinal hypopigmentation, vasculature changes, and decreased function

In their paper, “The microphthalmia-associated transcription factor (Mitf) gene and its role in regulating eye function,” García-Llorca et al use the Phoenix MICRON® IV to examine the outer eye appearance, retinal pigmentation, and retinal vasculature through fluorescein angiography to study several different mouse mutants. Combined with electroretinography and histology, the fundus images tell a story of how subtle genetic differences can result in large phenotypic differences.

Retinal degeneration causes visual impairment and blindness and can be caused by mutations in retinal cells including the photoreceptors and retinal pigment epithelium (RPE). The Mitf gene is involved in RPE differentiation and proliferation and mutations in the gene can lead to coat pigmentation abnormalities and inner ear and eye defects. Mutations are associated with the human diseases Waardenburg and Tietz syndrome and as well as small eye defects. García-Llorca et al study four Mitf mutant mice strains with normal eye size to examine the more subtle effects that an RPE gene abnormality might cause.

MITF Coat and eye appearance
Figure 1: Mitf coat and eye appearance. The outer eye is clearly visualized with the Phoenix MICRON® IV.

The four strains, with coat pigmentation and outer eye appearance shown in Figure 1, are: heterozygous Mitfmivga9/+, homozygous Mitfmienu22(398), heterozygous MitfMiWh/+, and MitfMiWh/Mitfmi. The heterozygous Mitfmivga9/+ and homozygous Mitfmienu22(398) had normal eye size, normal ERG responses, and mostly normal histology. However, the Phoenix MICRON® IV fundus images revealed that heterozygous Mitfmivga9/+ had discrete yellow lesions with normal vasculature while homozygous Mitfmienu22(398) had large unpigmented lesions with irregular borders and hyperfluorescent areas in fluorescein angiography, though normal capillaries (Fig 2). The other two mutants had much more dysfunction: no ERG responses with widespread retinal degeneration. The Phoenix MICRON® IV images showed that the heterozygous MitfMiWh/+ had hypopigmented retinas with large lack of pigmentation and reduced capillaries while the MitfMiWh/Mitfmi had eye dilation problems and a widespread lack of pigmentation in the retina (Fig 2).

fundus pigmentation and retinal vasculature
Figure 2. The fundus pigmentation and retinal vasculature differences among the various Mitf mutants. Images taken with the Phoenix MICRON® IV.

As the authors write, “This study provides more evidence that a functional RPE is important for normal photoreceptor function,” as Mitf is RPE-specific and not expressed in the neuroretina. The RPE is essential for normal retinal structure and function and studies such as these examining the various genetic factors affecting the RPE clarify the role of the RPE in normal and dysfunctional eyes.

García-Llorca, A., Aspelund, S. G., Ogmundsdottir, M. H., Steingrimsson, E., & Eysteinsson, T. (2019). The microphthalmia-associated transcription factor ( Mitf ) gene and its role in regulating eye function. Scientific Reports,9(1), 1–12.