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 D.
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.
N1 - Funding Information:
This work was supported by Research to Prevent Blindness , International Foundation for Optic Nerve Diseases (IFOND) , Struggling Within Leber's , The Poincenot Family , the Eierman Foundation , and a National Eye Institute grant EY03040 (F.N.R.-C., B.X.P., and A.A.S.). The molecular investigations were performed at the Wilhelm Johannsen Centre for Functional Genome Research, established by the Danish National Research Foundation. The Lundbeck Foundation (grant no. 32011 ) and Widex A/S are acknowledged for the financial support to the Audiogenetic Research Group (L.T., N.D.R., and M.L.).
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.
KW - Axonal degeneration
KW - Leber hereditary optic neuropathy
KW - Myelin basic protein
KW - Optic nerve
KW - Retinal ganglion cell
KW - Wolfram Syndrome
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U2 - 10.1016/j.mito.2013.05.013
DO - 10.1016/j.mito.2013.05.013
M3 - Article
C2 - 23748048
AN - SCOPUS:84887015445
SN - 1567-7249
VL - 13
SP - 841
EP - 845
JO - Mitochondrion
JF - Mitochondrion
IS - 6
ER -