TY - JOUR
T1 - Enhanced Robustness of the Mouse Retinal Circadian Clock Upon Inherited Retina Degeneration
AU - Gegnaw, Shumet T.
AU - Sandu, Cristina
AU - Mazzaro, Nadia
AU - Mendoza, Jorge
AU - Bergen, Arthur A.
AU - Felder-Schmittbuhl, Marie-Paule
N1 - Funding Information: The authors thank Dr. Dominique Sage, Dr. Sophie Reibel, and Nicolas Lethenet for animal care and Dr. Jérôme Roger for rd10 mice. This project was funded with support from the NeuroTime Erasmus + Program of the European Commission and the Center National pour la Recherche Scientifique. Publisher Copyright: © 2022 The Author(s).
PY - 2022/10
Y1 - 2022/10
N2 - Daily biological rhythms are fundamental to retinal physiology and visual function. They are generated by a local circadian clock composed of a network of cell type/layer-specific, coupled oscillators. Animal models of retinal degeneration have been instrumental in characterizing the anatomical organization of the retinal clock. However, it is still unclear, among the multiple cell-types composing the retina, which ones are essential for proper circadian function. In this study, we used a previously well-characterized mouse model for autosomal dominant retinitis pigmentosa to examine the relationship between rod degeneration and the retinal circadian clock. This model carries the P23H mutation in rhodopsin, which induces mild rod degeneration in heterozygous and rapid loss of photoreceptors in homozygous genotypes. By measuring PER2::LUC bioluminescence rhythms, we show that the retinal clock in P23H/+ heterozygous mice displays circadian rhythms with significantly increased robustness and amplitude. By treating retinal explants with L-α aminoadipic acid, we further provide evidence that this enhanced rhythmicity might involve activation of Müller glial cells.
AB - Daily biological rhythms are fundamental to retinal physiology and visual function. They are generated by a local circadian clock composed of a network of cell type/layer-specific, coupled oscillators. Animal models of retinal degeneration have been instrumental in characterizing the anatomical organization of the retinal clock. However, it is still unclear, among the multiple cell-types composing the retina, which ones are essential for proper circadian function. In this study, we used a previously well-characterized mouse model for autosomal dominant retinitis pigmentosa to examine the relationship between rod degeneration and the retinal circadian clock. This model carries the P23H mutation in rhodopsin, which induces mild rod degeneration in heterozygous and rapid loss of photoreceptors in homozygous genotypes. By measuring PER2::LUC bioluminescence rhythms, we show that the retinal clock in P23H/+ heterozygous mice displays circadian rhythms with significantly increased robustness and amplitude. By treating retinal explants with L-α aminoadipic acid, we further provide evidence that this enhanced rhythmicity might involve activation of Müller glial cells.
KW - P23H
KW - PER2::LUC bioluminescence
KW - circadian clock
KW - photoreceptor
KW - retina
KW - retinitis pigmentosa
UR - http://www.scopus.com/inward/record.url?scp=85135231245&partnerID=8YFLogxK
U2 - https://doi.org/10.1177/07487304221112845
DO - https://doi.org/10.1177/07487304221112845
M3 - Article
C2 - 35912966
SN - 0748-7304
VL - 37
SP - 567
EP - 574
JO - Journal of biological rhythms
JF - Journal of biological rhythms
IS - 5
ER -