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.
authors.affiliation: Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Fred N
authors.initials: FN
authors.lastname: Ross-Cisneros
authors.forename: Billy X
authors.initials: BX
authors.lastname: Pan
authors.forename: Ruwan A
authors.initials: RA
authors.lastname: Silva
authors.forename: Neil R
authors.initials: NR
authors.lastname: Miller
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Albini
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Tranebjaerg
authors.forename: Nanna D
authors.initials: ND
authors.lastname: Rendtorff
authors.forename: Marianne
authors.initials: M
authors.lastname: Lodahl
authors.forename: Milton N
authors.initials: MN
authors.lastname: Moraes-Filho
authors.forename: Milton N
authors.initials: MN
authors.lastname: Moraes
authors.forename: Solange R
authors.initials: SR
authors.lastname: Salomao
authors.forename: Adriana
authors.initials: A
authors.lastname: Berezovsky
authors.forename: Rubens
authors.initials: R
authors.lastname: Belfort
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Sadun
mesh_terms: D000328:Adult; D001369:Axons; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D009900:Optic Nerve / Q000473:pathology*; D014929:Wolfram Syndrome / Q000473:pathology*
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein
keywords: Axonal degeneration; Leber hereditary optic neuropathy; Myelin basic protein; Optic nerve; Retinal ganglion cell; Wolfram Syndrome