Loss of Melanopsin-Expressing Ganglion Cell Subtypes and Dendritic Degeneration in the Aging Human Retina

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Title: Loss of Melanopsin-Expressing Ganglion Cell Subtypes and Dendritic Degeneration in the Aging Human Retina
Authors: Esquiva Sobrino, Gema | Lax, Pedro | Pérez-Santonja, Juan J. | García-Fernández, José M. | Cuenca, Nicolás
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: Retina | Melanopsin ganglion cells | Circadian rhythms | Immunohistochemistry | Retinal cell mosaics
Knowledge Area: Fisiología | Biología Celular
Issue Date: 4-Apr-2017
Publisher: Frontiers Media
Citation: Esquiva G, Lax P, Pérez-Santonja JJ, García-Fernández JM and Cuenca N (2017) Loss of Melanopsin-Expressing Ganglion Cell Subtypes and Dendritic Degeneration in the Aging Human Retina. Front. Aging Neurosci. 9:79. doi: 10.3389/fnagi.2017.00079
Abstract: In mammals, melanopsin-expressing retinal ganglion cells (mRGCs) are, among other things, involved in several non-image-forming visual functions, including light entrainment of circadian rhythms. Considering the profound impact of aging on visual function and ophthalmic diseases, here we evaluate changes in mRGCs throughout the life span in humans. In 24 post-mortem retinas from anonymous human donors aged 10–81 years, we assessed the distribution, number and morphology of mRGCs by immunostaining vertical retinal sections and whole-mount retinas with antibodies against melanopsin. Human retinas showed melanopsin immunoreactivity in the cell body, axon and dendrites of a subset of ganglion cells at all ages tested. Nearly half of the mRGCs (51%) were located within the ganglion cell layer (GCL), and stratified in the outer (M1, 12%) or inner (M2, 16%) margin of the inner plexiform layer (IPL) or in both plexuses (M3, 23%). M1 and M2 cells conformed fairly irregular mosaics, while M3 cell distribution was slightly more regular. The rest of the mRGCs were more regularly arranged in the inner nuclear layer (INL) and stratified in the outer margin of the IPL (M1d, 49%). The quantity of each cell type decrease after age 70, when the total number of mRGCs was 31% lower than in donors aged 30–50 years. Moreover, in retinas with an age greater than 50 years, mRGCs evidenced a decrease in the dendritic area that was both progressive and age-dependent, as well as fewer branch points and terminal neurite tips per cell and a smaller Sholl area. After 70 years of age, the distribution profile of the mRGCs was closer to a random pattern than was observed in younger retinas. We conclude that advanced age is associated with a loss in density and dendritic arborization of the mRGCs in human retinas, possibly accounting for the more frequent occurrence of circadian rhythm disorders in elderly persons.
Sponsor: This research was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO-FEDER BFU2015-67139-R), Instituto de Salud Carlos III (RETICS-FEDER RD16/0008/0016) and Generalitat Valenciana (PROMETEO/2016/158).
URI: http://hdl.handle.net/10045/65187
ISSN: 1663-4365
DOI: 10.3389/fnagi.2017.00079
Language: eng
Type: info:eu-repo/semantics/article
Rights: © 2017 Esquiva, Lax, Pérez-Santonja, García-Fernández and Cuenca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Peer Review: si
Publisher version: http://dx.doi.org/10.3389/fnagi.2017.00079
Appears in Collections:INV - NEUROVIS - Artículos de Revistas

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