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F.N. Ross–Cisneros, A.A. Sadun, P. Barboni, G. Plazzi, V. Carelli; Optic Nerve Histopathology in a Case of Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) with Visual System Disturbances. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1608.
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Purpose: To describe the light microscopic (LM) features of optic nerve tissue from a patient diagnosed with MNGIE, an autosomal recessive disease associated with mitochondrial DNA (mtDNA) alterations secondary to a homozygous G1443A mutation in the nuclear gene for thymidine phosphorylase (TP). The patient's recent clinical picture consisted of bilateral optic atrophy with optic disc cupping. The visual fields demonstrated general depression in a non–glaucomatous pattern. Visual disturbances associated with MNGIE are rare. Methods: Right (OD) and left (OS) ocular tissues were obtained at autopsy from the MNGIE patient and from age–matched controls . Horizontal profiles of optic nerve heads with some peri–papillary retina and cross–sections of retrobulbar optic nerves proximal to the globe were dissected from the posterior poles and immediately fixed in 10% neutral buffered formalin. The specimens were further dissected equally in half. One group was embedded in paraffin, sectioned at 5 microns, stained with hematoxylin and eosin (H&E) and periodic–acid Schiff (PAS) for general morphology, and immunohistochemically for myelin basic protein (MBP) to identify possible fiber loss postlaminarly. The other group was post–fixed in a buffered 2% paraformaldehyde/glutaraldehyde solution and embedded in epon to perform future ultrastructural studies. Results: LM examination of the OD and OS optic nerve heads from the MNGIE patient stained with H&E and PAS showed both a tilt and mild glaucomatous cupping (with an intact rim). Morphological assessment of the MNGIE optic nerves from cross–sectional profiles stained immunohistochemically with MBP revealed a complex pattern of fiber drop out involving primarily the nasal periphery, but there were also zones of loss within the temporal side. Controls were observed to be within normal limits. Conclusions: The pattern of axonal atrophy was very distinct from the temporal wedge/papillo–macular bundle loss typical for mitochondrial disorders such as Leber's Hereditary Optic Neuropathy (LHON) or Dominant Optic Atrophy (DOA). Glaucoma–like optic neuropathy has been previously reported in patients with mtDNA complex II defects. It is therefore likely that various types of mitochondrial deficiencies may present with different patterns of optic atrophy.
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