Age-related changes in photosensitive melanopsin-expressing retinal ganglion cells correlate with circadian rhythm impairments in sighted and blind rats

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Title: Age-related changes in photosensitive melanopsin-expressing retinal ganglion cells correlate with circadian rhythm impairments in sighted and blind rats
Authors: Lax, Pedro | Esquiva Sobrino, Gema | Fuentes-Broto, Lorena | Segura, Francisco | Sánchez Cano, Ana | Cuenca, Nicolás | Pinilla Lozano, Isabel
Research Group/s: Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS)
Center, Department or Service: Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología
Keywords: Aging | Neurodegenerative diseases | P23H rat | Retinitis pigmentosa
Knowledge Area: Fisiología | Biología Celular
Issue Date: 2016
Publisher: Taylor & Francis
Citation: Chronobiology International. 2016, 33(4): 374-391. doi:10.3109/07420528.2016.1151025
Abstract: The melanopsin system consists of intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (mRGCs). These mRGCs mediate several non-image-forming visual functions, including light entrainment of circadian rhythms. Here we evaluate age-related alterations of the melanopsin system and circadian rhythms in P23H line 1 (P23H-1) rats, a rodent model of retinitis pigmentosa (RP). In homozygous P23H-1 rats and wild-type control rats from the same genetic background (Sprague–Dawley), body temperature and locomotor activity were continuously monitored at 10-min intervals for 7 days, once every 4–5 weeks, between 2 and 24 months of age, using a telemetry transmitter. The distribution and number of mRGCs were assessed in control rats at 12, 18, and 24 months of age and in P23H-1 rats aged 12, 18, 24, and 30 months by immunostaining whole-mount retinas with antibodies against melanopsin. The mean density of mRGCs in control rats showed no significant variations when evaluated at 12 and 18 months of age, and fell by approximately 56% between 18 and 24 months of age. Meanwhile, a significant decrease in the mean number of mRGCs was found in 18-month-old P23H-1 rats as compared to 18-month-old control rats (81% decrease). Parametric and non-parametric analyses of the records showed a gradual age-dependent weakening of body temperature and locomotor activity circadian rhythms robustness in both control and P23H-1 rats from 2 to 24 months of age. However, body temperature and locomotor activity circadian patterns were less robust throughout the experiment in P23H-1 as compared to control rats, with lower amplitude, weaker coupling strength to environmental zeitgebers and higher fragmentation of the rhythms. The present study shows that the degeneration of photoreceptors and inner retinal neurons, characteristic of RP, has age-related degenerative effects on the melanopsin system and is associated with weaker circadian patterns.
Sponsor: This work is supported by the Spanish Ministry of Health [grant number FIS PI13-01124], the Spanish Ministry of Economy and Competitiveness [grant number MINECO-FEDER BFU2012-36845], Instituto de Salud Carlos III [grant number RETICS-FEDER RD12/0034/0010], Organización Nacional de Ciegos Españoles (ONCE), and FUNDALUCE.
ISSN: 0742-0528 (Print) | 1525-6073 (Online)
DOI: 10.3109/07420528.2016.1151025
Language: eng
Type: info:eu-repo/semantics/article
Rights: © 2016 Taylor & Francis
Peer Review: si
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Appears in Collections:INV - NEUROVIS - Artículos de Revistas

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