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 D. Rendtorff, Marianne Lodahl, Milton N. Moraes-Filho, Milton N. Moraes, Solange R. Salomao, Adriana Berezovsky, Rubens Belfort, Valerio Carelli, Alfredo A. Sadun

Research output: Contribution to journalArticle

13 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 languageEnglish
Pages (from-to)841-845
Number of pages5
JournalMitochondrion
Volume13
Issue number6
DOIs
Publication statusPublished - Nov 2013

Fingerprint

Wolfram Syndrome
Optic Nerve
Leber's Hereditary Optic Atrophy
Retina
Optic Nerve Diseases
Myelin Basic Protein
Optic Atrophy
Retinal Ganglion Cells
Hematoxylin
Eosine Yellowish-(YS)
Nose
Autopsy
Pathology

Keywords

  • Axonal degeneration
  • Leber hereditary optic neuropathy
  • Myelin basic protein
  • Optic nerve
  • Retinal ganglion cell
  • Wolfram Syndrome

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Molecular Medicine

Cite this

Ross-Cisneros, F. N., Pan, B. X., Silva, R. A., Miller, N. R., Albini, T. A., Tranebjaerg, L., ... 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

Optic nerve histopathology in a case of Wolfram Syndrome : A mitochondrial pattern of axonal loss. / Ross-Cisneros, Fred N.; Pan, Billy X.; Silva, Ruwan A.; Miller, Neil R.; Albini, Thomas A.; Tranebjaerg, Lisbeth; Rendtorff, Nanna D.; Lodahl, Marianne; Moraes-Filho, Milton N.; Moraes, Milton N.; Salomao, Solange R.; Berezovsky, Adriana; Belfort, Rubens; Carelli, Valerio; Sadun, Alfredo A.

In: Mitochondrion, Vol. 13, No. 6, 11.2013, p. 841-845.

Research output: Contribution to journalArticle

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
Ross-Cisneros FN, Pan BX, Silva RA, Miller NR, Albini TA, Tranebjaerg L et al. Optic nerve histopathology in a case of Wolfram Syndrome: A mitochondrial pattern of axonal loss. Mitochondrion. 2013 Nov;13(6):841-845. https://doi.org/10.1016/j.mito.2013.05.013
Ross-Cisneros, Fred N. ; Pan, Billy X. ; Silva, Ruwan A. ; Miller, Neil R. ; Albini, Thomas A. ; Tranebjaerg, Lisbeth ; Rendtorff, Nanna D. ; Lodahl, Marianne ; Moraes-Filho, Milton N. ; Moraes, Milton N. ; Salomao, Solange R. ; Berezovsky, Adriana ; Belfort, Rubens ; Carelli, Valerio ; Sadun, Alfredo A. / Optic nerve histopathology in a case of Wolfram Syndrome : A mitochondrial pattern of axonal loss. In: Mitochondrion. 2013 ; Vol. 13, No. 6. pp. 841-845.
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AU - Miller, Neil R.

AU - Albini, Thomas A.

AU - Tranebjaerg, Lisbeth

AU - Rendtorff, Nanna D.

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AU - Moraes-Filho, Milton N.

AU - Moraes, Milton N.

AU - Salomao, Solange R.

AU - Berezovsky, Adriana

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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.

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