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Mones S Abu-Asab, Yujuan Wang, Chi-Chao Chan, ; Mitochondrial Dysfunctions in Extraocular Muscles and Optic Nerves of Moebius Syndrome. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4440.
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Moebius syndrome is an extremely rare congenital neurological disorder of unknown etiology that primarily affects the 6th (abducens) and 7th (facial) cranial nerves causing motionless face and lateral immobility of the eyes. We have undertaken an ultrastructural approach to examine a case of Moebius syndrome in order to uncover the affected cellular organelles within the muscles and nerves as well as to infer their related biochemical pathways.
A postmortem ultrastructural examination was performed on 12 extraocular muscles, two optic nerves, and a superior oblique nerve of a Moebius patient. The patient was a 64 year old Caucasian woman with bilateral facial nerve palsy and partial abducens palsy. During the last 6 years of her life, she had bilateral ectropion, map-dot-fingerprint dystrophy, cataract, keratitis, lagophthalmos, and poor vision. The tissues were prepared for transmission electron microscopy.
All muscle fibers were punctuated with lipid droplets of various sizes. Mitochondria were abnormal in all specimens showing various degrees of edema, enlargement, dislocation, and disintegration of internal membrane and cristae; some mitochondria had internal lipid accumulation. Three different types of mitochondrial dysfunctions were identified in the extraocular muscles and nerves. Mitochondria with internal lipid accumulation pointed out to a dysfunctional beta-oxidation pathway, the main fat breakdown process of the cell. There were giant mitochondria that have been transformed into large aqueous storage vesicle, which was indicative of a dysfunctionality of a tricarboxylic acid (TCA) cycle enzyme. The third type of dysfunction is related to the second and was inferred from the numerous fat droplets within the muscle fibers. Accumulation of lipid droplets within the cytoplasm results from the excessive production of acetyl-Co-A in the mitochondria and their inability to metabolize it through the TCA cycle. Excess of acetyl-Co-A exits the mitochondria and is utilized in the cytoplasm for fatty acid synthesis.
The extraocular muscles as well as optic and lateral nerves of the Moebius patient exhibited three types of mitochondrial dysfunctions that occurred within the TCA cycle and beta-oxidation pathway. Such biochemical aberrations within the mitochondria suggest the possibility that Moebius syndrome etiology may be mitochondrial in origin.
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