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

Detalhes bibliográficos
Autor(a) principal: La Morgia, Chiara
Data de Publicação: 2010
Outros Autores: Ross-Cisneros, Fred N., Sadun, Alfredo A., Hannibal, Jens, Munarini, Alessandra, Mantovani, Vilma, Barboni, Piero, Cantalupo, Gaetano, Tozer, Kevin R., Sancisi, Elisa, Salomão, Solange Rios [UNIFESP], Moraes, Milton Nunes de [UNIFESP], Moraes-Filho, Milton Nunes de [UNIFESP], Heegaard, Steffen, Milea, Dan, Kjer, Poul, Montagna, Pasquale, Carelli, Valerio
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.1093/brain/awq155
http://repositorio.unifesp.br/handle/11600/32740
Resumo: 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.
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spelling Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathiescircadian rhythmsneuro-ophthalmologymitochondrial diseasesLHONneuropathologyMitochondrial 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.Univ Bologna, Dept Neurol Sci, I-40127 Bologna, ItalyUniv So Calif, Keck Sch Med, Doheny Eye Inst, Dept Ophthalmol, Los Angeles, CA 90033 USAUniv Copenhagen, Bispebjerg Hosp, Dept Clin Biochem, DK-2400 Copenhagen, DenmarkUniv Copenhagen, Rigshosp, DK-2400 Copenhagen, DenmarkS Orsola Malpighi Univ Hosp, Biomed Ctr Appl Res CRBA, I-40138 Bologna, ItalyUniv Parma, Dept Neurosci, I-43125 Parma, ItalyUniversidade Federal de São Paulo, UNIFESP, Dept Ophthalmol, BR-04023900 São Paulo, BrazilUniv Copenhagen, Eye Pathol Sect, Dept Neurosci & Pharmacol, DK-2200 Copenhagen, DenmarkCopenhagen Univ Hosp, DK-2600 Copenhagen, DenmarkAngers Univ Hosp, Dept Ophthalmol, F-49033 Angers, FranceUniversidade Federal de São Paulo, UNIFESP, Dept Ophthalmol, BR-04023900 São Paulo, BrazilWeb of ScienceTelethon-ItalyInternational Foundation for Optic Nerve DiseasesResearch to Prevent BlindnessStruggling Within Leber's FoundationNational Institutes of HealthErmian FoundationTelethon-Italy: GGP06233National Institutes of Health: EY03040Oxford Univ PressUniv BolognaUniv So CalifUniv CopenhagenS Orsola Malpighi Univ HospUniv ParmaUniversidade Federal de São Paulo (UNIFESP)Copenhagen Univ HospAngers Univ HospLa Morgia, ChiaraRoss-Cisneros, Fred N.Sadun, Alfredo A.Hannibal, JensMunarini, AlessandraMantovani, VilmaBarboni, PieroCantalupo, GaetanoTozer, Kevin R.Sancisi, ElisaSalomão, Solange Rios [UNIFESP]Moraes, Milton Nunes de [UNIFESP]Moraes-Filho, Milton Nunes de [UNIFESP]Heegaard, SteffenMilea, DanKjer, PoulMontagna, PasqualeCarelli, Valerio2016-01-24T14:05:13Z2016-01-24T14:05:13Z2010-08-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion2426-2438http://dx.doi.org/10.1093/brain/awq155Brain. Oxford: Oxford Univ Press, v. 133, p. 2426-2438, 2010.10.1093/brain/awq1550006-8950http://repositorio.unifesp.br/handle/11600/32740WOS:000280982700021engBraininfo:eu-repo/semantics/openAccesshttp://www.oxfordjournals.org/access_purchase/self-archiving_policyb.htmlreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2022-02-07T21:52:44Zoai:repositorio.unifesp.br/:11600/32740Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652022-02-07T21:52:44Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies
title Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies
spellingShingle Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies
La Morgia, Chiara
circadian rhythms
neuro-ophthalmology
mitochondrial diseases
LHON
neuropathology
title_short Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies
title_full Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies
title_fullStr Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies
title_full_unstemmed Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies
title_sort Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies
author La Morgia, Chiara
author_facet La Morgia, Chiara
Ross-Cisneros, Fred N.
Sadun, Alfredo A.
Hannibal, Jens
Munarini, Alessandra
Mantovani, Vilma
Barboni, Piero
Cantalupo, Gaetano
Tozer, Kevin R.
Sancisi, Elisa
Salomão, Solange Rios [UNIFESP]
Moraes, Milton Nunes de [UNIFESP]
Moraes-Filho, Milton Nunes de [UNIFESP]
Heegaard, Steffen
Milea, Dan
Kjer, Poul
Montagna, Pasquale
Carelli, Valerio
author_role author
author2 Ross-Cisneros, Fred N.
Sadun, Alfredo A.
Hannibal, Jens
Munarini, Alessandra
Mantovani, Vilma
Barboni, Piero
Cantalupo, Gaetano
Tozer, Kevin R.
Sancisi, Elisa
Salomão, Solange Rios [UNIFESP]
Moraes, Milton Nunes de [UNIFESP]
Moraes-Filho, Milton Nunes de [UNIFESP]
Heegaard, Steffen
Milea, Dan
Kjer, Poul
Montagna, Pasquale
Carelli, Valerio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv 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
dc.contributor.author.fl_str_mv La Morgia, Chiara
Ross-Cisneros, Fred N.
Sadun, Alfredo A.
Hannibal, Jens
Munarini, Alessandra
Mantovani, Vilma
Barboni, Piero
Cantalupo, Gaetano
Tozer, Kevin R.
Sancisi, Elisa
Salomão, Solange Rios [UNIFESP]
Moraes, Milton Nunes de [UNIFESP]
Moraes-Filho, Milton Nunes de [UNIFESP]
Heegaard, Steffen
Milea, Dan
Kjer, Poul
Montagna, Pasquale
Carelli, Valerio
dc.subject.por.fl_str_mv circadian rhythms
neuro-ophthalmology
mitochondrial diseases
LHON
neuropathology
topic circadian rhythms
neuro-ophthalmology
mitochondrial diseases
LHON
neuropathology
description 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.
publishDate 2010
dc.date.none.fl_str_mv 2010-08-01
2016-01-24T14:05:13Z
2016-01-24T14:05:13Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1093/brain/awq155
Brain. Oxford: Oxford Univ Press, v. 133, p. 2426-2438, 2010.
10.1093/brain/awq155
0006-8950
http://repositorio.unifesp.br/handle/11600/32740
WOS:000280982700021
url http://dx.doi.org/10.1093/brain/awq155
http://repositorio.unifesp.br/handle/11600/32740
identifier_str_mv Brain. Oxford: Oxford Univ Press, v. 133, p. 2426-2438, 2010.
10.1093/brain/awq155
0006-8950
WOS:000280982700021
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Brain
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
http://www.oxfordjournals.org/access_purchase/self-archiving_policyb.html
eu_rights_str_mv openAccess
rights_invalid_str_mv http://www.oxfordjournals.org/access_purchase/self-archiving_policyb.html
dc.format.none.fl_str_mv 2426-2438
dc.publisher.none.fl_str_mv Oxford Univ Press
publisher.none.fl_str_mv Oxford Univ Press
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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