Optic nerve histopathology in a case of Wolfram Syndrome: A mitochondrial pattern of axonal loss

Fred N Ross-Cisneros; Billy X Pan; Ruwan A Silva; Neil R Miller; Thomas A Albini; Lisbeth Tranebjaerg; Nanna Dahl Rendtorff; Marianne Lodahl; Milton N Moraes-Filho; Milton N Moraes; Solange R Salomao; Adriana Berezovsky; Rubens Belfort; Valerio Carelli; Alfredo A Sadun

doi:10.1016/j.mito.2013.05.013

Optic nerve histopathology in a case of Wolfram Syndrome: A mitochondrial pattern of axonal loss

Fred N Ross-Cisneros, Billy X Pan, Ruwan A Silva, Neil R Miller, Thomas A Albini, Lisbeth Tranebjaerg, Nanna Dahl Rendtorff, Marianne Lodahl, Milton N Moraes-Filho, Milton N Moraes, Solange R Salomao, Adriana Berezovsky, Rubens Belfort, Valerio Carelli, Alfredo A Sadun

18 Citations (Scopus)

Abstract

Mitochondrial dysfunction in Wolfram Syndrome (WS) is controversial and optic neuropathy, a cardinal clinical manifestation, is poorly characterized. We here describe the histopathological features in postmortem retinas and optic nerves (ONs) from one patient with WS, testing the hypothesis that mitochondrial dysfunction underlies the pathology. Eyes and retrobulbar ONs were obtained at autopsy from a WS patient, and compared with those of a Leber hereditary optic neuropathy (LHON) patient and one healthy control. Retinas were stained with hematoxylin & eosin for general morphology and ONs were immunostained for myelin basic protein (MBP). Immunostained ONs were examined in four "quadrants": superior, inferior, nasal, and temporal. The WS retinas displayed a severe loss of retinal ganglion cells in the macular region similar to the LHON retina, but not in the control. The WS ONs, immunostained for MBP, revealed a zone of degeneration in the temporal and inferior quadrants. This pattern was similar to that seen in the LHON ONs but not in the control. Thus, the WS patient displayed a distinct pattern of optic atrophy observed bilaterally in the temporal and inferior quadrants of the ONs. This arrangement of axonal degeneration, involving primarily the papillomacular bundle, closely resembled LHON and other mitochondrial optic neuropathies, supporting that mitochondrial dysfunction underlies its pathogenesis.

Original language	English
Journal	Mitochondrion
Volume	13
Issue number	6
Pages (from-to)	841-845
Number of pages	5
ISSN	1567-7249
DOIs	https://doi.org/10.1016/j.mito.2013.05.013
Publication status	Published - Nov 2013

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Ross-Cisneros, F. N., Pan, B. X., Silva, R. A., Miller, N. R., Albini, T. A., Tranebjaerg, L., Rendtorff, N. D., Lodahl, M., Moraes-Filho, M. N., Moraes, M. N., Salomao, S. R., Berezovsky, A., Belfort, R., Carelli, V., & Sadun, A. A. (2013). Optic nerve histopathology in a case of Wolfram Syndrome: A mitochondrial pattern of axonal loss. Mitochondrion, 13(6), 841-845. https://doi.org/10.1016/j.mito.2013.05.013

Ross-Cisneros, FN, Pan, BX, Silva, RA, Miller, NR, Albini, TA, Tranebjaerg, L, Rendtorff, ND, Lodahl, M, Moraes-Filho, MN, Moraes, MN, Salomao, SR, Berezovsky, A, Belfort, R, Carelli, V & Sadun, AA 2013, 'Optic nerve histopathology in a case of Wolfram Syndrome: A mitochondrial pattern of axonal loss', Mitochondrion, vol. 13, no. 6, pp. 841-845. https://doi.org/10.1016/j.mito.2013.05.013

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title = "Optic nerve histopathology in a case of Wolfram Syndrome: A mitochondrial pattern of axonal loss",

abstract = "Mitochondrial dysfunction in Wolfram Syndrome (WS) is controversial and optic neuropathy, a cardinal clinical manifestation, is poorly characterized. We here describe the histopathological features in postmortem retinas and optic nerves (ONs) from one patient with WS, testing the hypothesis that mitochondrial dysfunction underlies the pathology. Eyes and retrobulbar ONs were obtained at autopsy from a WS patient, and compared with those of a Leber hereditary optic neuropathy (LHON) patient and one healthy control. Retinas were stained with hematoxylin & eosin for general morphology and ONs were immunostained for myelin basic protein (MBP). Immunostained ONs were examined in four {"}quadrants{"}: superior, inferior, nasal, and temporal. The WS retinas displayed a severe loss of retinal ganglion cells in the macular region similar to the LHON retina, but not in the control. The WS ONs, immunostained for MBP, revealed a zone of degeneration in the temporal and inferior quadrants. This pattern was similar to that seen in the LHON ONs but not in the control. Thus, the WS patient displayed a distinct pattern of optic atrophy observed bilaterally in the temporal and inferior quadrants of the ONs. This arrangement of axonal degeneration, involving primarily the papillomacular bundle, closely resembled LHON and other mitochondrial optic neuropathies, supporting that mitochondrial dysfunction underlies its pathogenesis.",

author = "Ross-Cisneros, {Fred N} and Pan, {Billy X} and Silva, {Ruwan A} and Miller, {Neil R} and Albini, {Thomas A} and Lisbeth Tranebjaerg and Rendtorff, {Nanna Dahl} and Marianne Lodahl and Moraes-Filho, {Milton N} and Moraes, {Milton N} and Salomao, {Solange R} and Adriana Berezovsky and Rubens Belfort and Valerio Carelli and Sadun, {Alfredo A}",

year = "2013",

month = nov,

doi = "10.1016/j.mito.2013.05.013",

language = "English",

volume = "13",

pages = "841--845",

journal = "Mitochondrion",

issn = "1567-7249",

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TY - JOUR

T1 - Optic nerve histopathology in a case of Wolfram Syndrome

T2 - A mitochondrial pattern of axonal loss

AU - Ross-Cisneros, Fred N

AU - Pan, Billy X

AU - Silva, Ruwan A

AU - Miller, Neil R

AU - Albini, Thomas A

AU - Tranebjaerg, Lisbeth

AU - Rendtorff, Nanna Dahl

AU - Lodahl, Marianne

AU - Moraes-Filho, Milton N

AU - Moraes, Milton N

AU - Salomao, Solange R

AU - Berezovsky, Adriana

AU - Belfort, Rubens

AU - Carelli, Valerio

AU - Sadun, Alfredo A

PY - 2013/11

Y1 - 2013/11

N2 - Mitochondrial dysfunction in Wolfram Syndrome (WS) is controversial and optic neuropathy, a cardinal clinical manifestation, is poorly characterized. We here describe the histopathological features in postmortem retinas and optic nerves (ONs) from one patient with WS, testing the hypothesis that mitochondrial dysfunction underlies the pathology. Eyes and retrobulbar ONs were obtained at autopsy from a WS patient, and compared with those of a Leber hereditary optic neuropathy (LHON) patient and one healthy control. Retinas were stained with hematoxylin & eosin for general morphology and ONs were immunostained for myelin basic protein (MBP). Immunostained ONs were examined in four "quadrants": superior, inferior, nasal, and temporal. The WS retinas displayed a severe loss of retinal ganglion cells in the macular region similar to the LHON retina, but not in the control. The WS ONs, immunostained for MBP, revealed a zone of degeneration in the temporal and inferior quadrants. This pattern was similar to that seen in the LHON ONs but not in the control. Thus, the WS patient displayed a distinct pattern of optic atrophy observed bilaterally in the temporal and inferior quadrants of the ONs. This arrangement of axonal degeneration, involving primarily the papillomacular bundle, closely resembled LHON and other mitochondrial optic neuropathies, supporting that mitochondrial dysfunction underlies its pathogenesis.

AB - Mitochondrial dysfunction in Wolfram Syndrome (WS) is controversial and optic neuropathy, a cardinal clinical manifestation, is poorly characterized. We here describe the histopathological features in postmortem retinas and optic nerves (ONs) from one patient with WS, testing the hypothesis that mitochondrial dysfunction underlies the pathology. Eyes and retrobulbar ONs were obtained at autopsy from a WS patient, and compared with those of a Leber hereditary optic neuropathy (LHON) patient and one healthy control. Retinas were stained with hematoxylin & eosin for general morphology and ONs were immunostained for myelin basic protein (MBP). Immunostained ONs were examined in four "quadrants": superior, inferior, nasal, and temporal. The WS retinas displayed a severe loss of retinal ganglion cells in the macular region similar to the LHON retina, but not in the control. The WS ONs, immunostained for MBP, revealed a zone of degeneration in the temporal and inferior quadrants. This pattern was similar to that seen in the LHON ONs but not in the control. Thus, the WS patient displayed a distinct pattern of optic atrophy observed bilaterally in the temporal and inferior quadrants of the ONs. This arrangement of axonal degeneration, involving primarily the papillomacular bundle, closely resembled LHON and other mitochondrial optic neuropathies, supporting that mitochondrial dysfunction underlies its pathogenesis.

U2 - 10.1016/j.mito.2013.05.013

DO - 10.1016/j.mito.2013.05.013

M3 - Journal article

C2 - 23748048

SN - 1567-7249

VL - 13

SP - 841

EP - 845

JO - Mitochondrion

JF - Mitochondrion

IS - 6

ER -

Optic nerve histopathology in a case of Wolfram Syndrome: A mitochondrial pattern of axonal loss

Abstract

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