Association of Optic Nerve Hypoplasia With Mitochondrial Cytopathies

Abstract

Ocular complications are common in the mitochondrial cytopathies and include optic atrophy and retinal degeneration. We retrospectively reviewed 80 patients with nonsyndromic mitochondrial cytopathies (ie, not Kearns-Sayre syndrome, myoclonus epilepsy associated with ragged red fibers [MERRF], mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes [MELAS], neuropathy ataxia and retinitis pigmentosa, Leigh disease, maternally inherited diabetes and deafness, and myoneurogastrointestinal disorder and encephalopathy) and found 10 cases of optic nerve hypoplasia. Optic nerve hypoplasia occurs in at least 12% of patients with nonsyndromic mitochondrial cytopathies. Although the exact pathogenesis of optic nerve hypoplasia in the context of mitochondrial cytopathy is unknown, we postulate that it is the result of excessive apoptosis during embryonic ganglion cell and/or axonal development from abnormal mitochondrial function and cellular energy metabolism. (J Child Neurol 2006;21:956—960; DOI 10.2310/7010.2006.00240).

Get full access to this article

View all access options for this article.

References

ZionV. : Opticnervehypoplasia. OphthalmicSemin 1976 ;1:171-196.

Nelson M. , Lessell S. , Sadun AA : Optic nerve hypoplasia and maternal diabetes mellitus. Arch Neurol 1986;43:20—25.

Zeki SM , Dutton GN : Optic nerve hypoplasia in children. Br J Ophthalmol 1990;74:300—304.

Phillips PH , Newman NJ : Mitochondrial diseases in pediatric ophthalmology. J AAPOS 1997;1:115—122.

Mosier MA , Lieberman MF , Green WR , Knox DL : Hypoplasia of the optic nerve. Arch Ophthalmol 1978;96:1437—1442.

Scheie HG , Adler FH : Aplasia of optic nerve. Arch Ophthalmol 1941 ;26:61.

Little LE , Whitmore PV, Wells TWJr: Aplasia of the optic nerve. J Pediatr Ophthalmol 1976;13:84—88.

Weiter JJ , McLean IW , Zimmerman LE : Aplasia of the optic nerve and disk. Am J Ophthalmol 1977;83:569—576.

Hotchkiss ML , Green WR : Optic nerve aplasia and hypoplasia. J Pediatr Ophthalmol Strabismus 1979;16:225—240.

10.

Provis JM , Vandriel P. , Billson FA , Russell P. : Human fetal optic nerve: Overproduction and elimination of retinal axons during development. J Comp Neurol 1985;238:92—100.

11.

Rakic P. : Prenatal genesis of connections subserving ocular dominance in the rhesus monkey. Nature 1976;261:467—471.

12.

Hoyt CG , Good WV : Do we really understand the difference between optic nerve hypoplasia and atrophy? Eye 1992;6:201—204.

13.

Frisen L. , Holmegaard L. : Spectrum of optic nerve hypoplasia. Br J Ophthalmol 1978;62:7—15.

14.

Sadun AA : Metabolic optic neuropathies. Metabolic optic neuropathies. Semin Ophthalmol 2002, 17:29—32.

15.

Finsterer J. : Mitochondriopathies. EurJNeurol 2004;11:163-186.

16.

Stromland K. : Ocular abnormalities in fetal alcohol syndrome . Acta Ophthalmol 1985;63:171.

17.

Baruah J. , Kinder D. : Ethanol induced ``mitochondrial cytopathy.'' Exp Pathol 1986;30:189—190.

18.

Chang TS , Johns DR , Walker D. , et al: Ocular clinicopathologic study of the mitochondrial encephalomyopathy overlap syndromes. Arch Ophthalmol 1993;111:1254—1262.

19.

Xu Y. , Liu P. , Li Y. : Impaired development of mitochondria plays a role in the central nervous system defects of fetal alcohol syndrome. Birth Defects Res 2005;73:83—91.

20.

Peng Y. , Yang PH , Guo Y. , et al: Catalase and peroxiredoxin 5 protect Xenopus embryos against alcohol-induced ocular anomalies. Invest Ophthalmol Vis Sci 2004;45:23—29.

21.

de la Monte SM , Wands JR : Chronic gestational exposure to ethanol impairs insulin-stimulated survival and mitochondrial function in cerebellar neurons . Cell Mol Life Sci 2002;59:882—893.

22.

de la Monte, Wands JR : Mitochondrial DNA damage and impaired mitochondrial function contribute to apoptosis of insulin-stimulated ethanol-exposed neuronal cells. Alcohol Clin Exp Res 2001;25:898—906.

23.

Vaudry D. , Rousselle C. , Basille M. , et al: Pituitary adenylate cyclase-activating polypeptide protects rat cerebellar granule neurons against ethanol-induced apoptotic cell death . PNAS 2002; 99:6398—6403.

24.

Boor R. , Rochels R. , Walther B. , Reitter B. : Aplasia of the retinal vessels combined with optic nerve hypoplasia, neonatal epileptic seizures, and lactic acidosis due to mitochondrial complex I deficiency . Eur J Pediatr 1992;151:519—521.

25.

Biousse V. , Pardue MT , Wallace DC , Newman NJ : The eyes of mito-mouse: Mouse models of mitochondrial disease. J Neuroophthalmol 2002;22:279—85.