Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies

Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies

Author La Morgia, Chiara Google Scholar
Ross-Cisneros, Fred N. Google Scholar
Sadun, Alfredo A. Google Scholar
Hannibal, Jens Google Scholar
Munarini, Alessandra Google Scholar
Mantovani, Vilma Google Scholar
Barboni, Piero Google Scholar
Cantalupo, Gaetano Google Scholar
Tozer, Kevin R. Google Scholar
Sancisi, Elisa Google Scholar
Salomão, Solange Rios Autor UNIFESP Google Scholar
Moraes, Milton Nunes de Autor UNIFESP Google Scholar
Moraes-Filho, Milton Nunes de Autor UNIFESP Google Scholar
Heegaard, Steffen Google Scholar
Milea, Dan Google Scholar
Kjer, Poul Google Scholar
Montagna, Pasquale Google Scholar
Carelli, Valerio Google Scholar
Institution Univ Bologna
Univ So Calif
Univ Copenhagen
S Orsola Malpighi Univ Hosp
Univ Parma
Universidade Federal de São Paulo (UNIFESP)
Copenhagen Univ Hosp
Angers Univ Hosp
Abstract Mitochondrial optic neuropathies, that is, Leber hereditary optic neuropathy and dominant optic atrophy, selectively affect retinal ganglion cells, causing visual loss with relatively preserved pupillary light reflex. the mammalian eye contains a light detection system based on a subset of retinal ganglion cells containing the photopigment melanopsin. These cells give origin to the retinohypothalamic tract and support the non-image-forming visual functions of the eye, which include the photoentrainment of circadian rhythms, light-induced suppression of melatonin secretion and pupillary light reflex. We studied the integrity of the retinohypothalamic tract in five patients with Leber hereditary optic neuropathy, in four with dominant optic atrophy and in nine controls by testing the light-induced suppression of nocturnal melatonin secretion. This response was maintained in optic neuropathy subjects as in controls, indicating that the retinohypothalamic tract is sufficiently preserved to drive light information detected by melanopsin retinal ganglion cells. We then investigated the histology of post-mortem eyes from two patients with Leber hereditary optic neuropathy and one case with dominant optic atrophy, compared with three age-matched controls. On these retinas, melanopsin retinal ganglion cells were characterized by immunohistochemistry and their number and distribution evaluated by a new protocol. in control retinas, we show that melanopsin retinal ganglion cells are lost with age and are more represented in the parafoveal region. in patients, we demonstrate a relative sparing of these cells compared with the massive loss of total retinal ganglion cells, even in the most affected areas of the retina. Our results demonstrate that melanopsin retinal ganglion cells resist neurodegeneration due to mitochondrial dysfunction and maintain non-image-forming functions of the eye in these visually impaired patients. We also show that in normal human retinas, these cells are more concentrated around the fovea and are lost with ageing. the current results provide a plausible explanation for the preservation of pupillary light reaction despite profound visual loss in patients with mitochondrial optic neuropathy, revealing the robustness of melanopsin retinal ganglion cells to a metabolic insult and opening the question of mechanisms that might protect these cells.
Keywords circadian rhythms
mitochondrial diseases
Language English
Sponsor Telethon-Italy
International Foundation for Optic Nerve Diseases
Research to Prevent Blindness
Struggling Within Leber's Foundation
National Institutes of Health
Ermian Foundation
Grant number Telethon-Italy: GGP06233
National Institutes of Health: EY03040
Date 2010-08-01
Published in Brain. Oxford: Oxford Univ Press, v. 133, p. 2426-2438, 2010.
ISSN 0006-8950 (Sherpa/Romeo, impact factor)
Publisher Oxford Univ Press
Extent 2426-2438
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000280982700021

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