Photoreceptor Degeneration in Homozygous Male Per2(luc) Mice During Aging

• Type of Material: Article
• Authors: Varunika Goyal, Morehouse School of Medicine; Christopher DeVera, Morehouse School of Medicine; Kenkichi Baba, Morehouse School of Medicine; Jana Sellers, Emory University; Micah A Chrenek, Emory University; Paul Iuvone, Emory University; Gianluca Tosini, Emory University
• Language: English
• Date: 2020-11-02
• Publisher: SAGE PUBLICATIONS INC
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 The Author(s).
• Final Published Version (URL): http://dx.doi.org/10.1177/0748730420965285
• Title of Journal or Parent Work: JOURNAL OF BIOLOGICAL RHYTHMS
• Volume: 36
• Issue: 2
• Start Page: 137
• End Page: 145
• Grant/Funding Information: This work was supported by National Institutes of Health Grants: GM116760 to K.B.; EY026291to G.T. and NS083932 to Morehouse School of Medicine; EY004864, EY027711, and EY006360 to P.M.I.; and an unrestricted departmental grant from Research to Prevent Blindness (Emory Department of Ophthalmology).
• Keywords: mice; Life Sciences & Biomedicine - Other Topics; retinal pigment epithelium; Life Sciences & Biomedicine; photoreceptors; Science & Technology; circadian; Biology; Physiology; aging; Per2(luc)

Abstract

The Per2luc mouse model developed by Takahashi laboratory is one of the most powerful models to study circadian rhythms in real time. In this study, we report that photoreceptors degenerate in male Per2luc mice during aging. Young (2.5- to 5-month-old) and aged (11- to 13.5-month-old) homozygous male Per2luc mice and C57BL/6J mice were used for this study. Retina structure and function were investigated via spectral domain optical coherence tomography (SD-OCT), fundus imaging, and electroretinography (ERG). Zonula occludens-1 (ZO-1) immunofluorescence was used to analyze the retinal pigment epithelium (RPE) morphology. Fundus examination revealed no difference between young Per2luc and wild-type (WT) mice. However, the fundus of aged Per2luc mice showed white deposits, suggestive of age-related drusen-like formation or microglia, which were absent in age-matched WT mice. No differences in retinal structure and function were observed between young Per2luc and WT mice. However, with age, Per2luc mice showed a significant reduction in total retinal thickness with respect to C57BL/6J mice. The reduction was mostly confined to the photoreceptor layer. Consistent with these results, we observed a significant decrease in the amplitude of a- and b-waves of the ERG in aged Per2luc mice. Analysis of the RPE morphology revealed that in aged Per2luc mice there was an increase in compactness and eccentricity with a decrease in solidity with respect to the values observed in WT, pointing toward signs of aging in the RPE of Per2luc mice. Our data demonstrate that homozygous Per2luc mice show photoreceptor degeneration during aging and a premature aging of the RPE.