Myo/Nog Cells are Phagocytotic and Increase in Number in Response to Photoreceptor Death in the Murine Model of Retinitis Pigmentosa

Abstract

Purpose : Myo/Nog cells play an essential role in normal eye development. Previous studies have shown that they migrate to areas of stress and injury in the retina and are neuroprotective, but their specific role in these areas of stress is unclear. In this study, we observed the behavior of Myo/Nog cells in a congenital murine model of retinitis pigmentosa (C3H mice), which results in the loss of photoreceptor cells within the outer nuclear layer of the retina (ONL).

Methods : C57BL/6J (C57) and C3H/HeJ (C3H) mice were assessed at weeks 2.5, 3, 4, 5, and 6 using scotopic electroretinography (ERG) and histological analysis. Enucleated eyes were fixed in paraformaldehyde and cryo-sectioned. Cryosections were labeled with Myo/Nog specific monoclonal antibodies and TUNEL to detect cell death; and analyzed by fluorescence microscopy.

Results : The decreased amplitude of the A and B waves in the C3H mice in comparison to those of C57 mice was verified with ERG (p<0.05) Progressive thinning of the retina in the C3H mice was confirmed by microscopic analysis. While C3H mice initially demonstrated a greater number of photoreceptors at the edge of the retina, by week 4 there were significantly fewer photoreceptors at the periphery in comparison to the mid-periphery and central retina (p<0.05). Myo/Nog cells were significantly more numerous in C3H than C57 retinas (p<0.05). The majority of Myo/Nog cells were found in the diminishing ONL and choroid. Several of the Myo/Nog cells had phagocytosed apoptotic photoreceptors.

Conclusions : Progressive retinal degeneration and visual deterioration in C3H mice are accompanied by an increase in Myo/Nog cells. They accumulate in parallel with an increase in cell death in the ONL and demonstrate phagocytic properties as they engulf dying cells. These findings are consistent with Myo/Nog cells’ behaviors in other forms of retinopathy and injury in other tissues. Future studies will characterize additional functions of Myo/Nog cells in this severe model of retinitis pigmentosa.

This is a 2021 ARVO Annual Meeting abstract.