Abstract
Purpose :
To test that Nr2e3-deficient rd7 mice with cone-like rod photoreceptors (“cods”) and enhanced S-cone density, have greater-than-wildtype (WT) mitochondria activity in vivo.
Methods :
4 mo WT and rd7 mice were studied. Minimum intensity projection OCT images mitigated outer retinal whorls and rosettes were generated to measure: i) the external limiting membrane - retinal pigment epithelium (ELM-RPE) thickness, a proxy for energy-dependent pH-triggered water removal, and ii) the Mitochondrial Configuration within Photoreceptors based on the profile shape Aspect Ratio (MCP/AR) of the hyperreflective band posterior to the ELM. Rod ellipsoid mitochondria distribution (electron microscopy, EM), retinal laminar thicknesses (OCT), and visual performance indices (optokinetic tracking) were also assessed.
Results :
ELM-RPE thickness in rd7 mice was lower than in WT mice, and unresponsive to dark-light conditions (unlike WT mice). rd7 mice also showed larger-than-WT mitochondria (EM). Together, these results imply high photoreceptor energy output. Also, rd7 mice had mitochondria that were more widely distributed than WT in inferior retina – but not superior retina - as measured by MCP/AR and EM. Functionally, inferior retina showed no light-dark MCP/AR difference in rd7 mice, unlike superior MCP/AR, and inferior and superior in WT mice. Modest outer nuclear layer thinning, together with thickening of the inner nuclear and inner plexiform layers, were noted in rd7 vs. WT mice. rd7 mice had visual performance indices matching WT mice.
Conclusions :
These data raise the possibility of greater-than-WT rod mitochondria activity in young Nr2e3-deficient mice, potentially underpinning their remarkable photoreceptor neuroprotection in retinitis pigmentosa models.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.