Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , , , , , , , , , , , , , , , |
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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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 |
_version_ |
1814268328781283328 |