Pathological confirmation of optic neuropathy in familial dysautonomia

Carlos E. Mendoza-Santiesteban, Jose Alberto Palma, Thomas R. Hedges, Nora V. Laver, Nada Farhat, Lucy Norcliffe-Kaufmann, Horacio Kaufmann

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Clinical data suggest that optic neuropathy and retinal ganglion cell loss are the main cause of visual decline in patients with familial dysautonomia, but this has not previously been confirmed by pathological analyses. We studied retinas and optic nerves in 6 eyes from 3 affected patients obtained at autopsy. Analyses included routine neurohistology and immunohistochemistry for neurofilaments, cytochrome c oxidase (COX), and melanopsin-containing ganglion cells. We observed profound axon loss in the temporal portions of optic nerves with relative preservation in the nasal portions; this correlated with clinical and optical coherence tomography findings in 1 patient. Retinal ganglion cell layers were markedly reduced in the central retina, whereas melanopsin-containing ganglion cells were relatively spared. COX staining was reduced in the temporal portions of the optic nerve indicating reduced mitochondrial density. Axonal swelling with degenerating lysosomes and mitochondria were observed by electron microscopy. These findings support the concept that there is a specific optic neuropathy and retinopathy in patients with familial dysautonomia similar to that seen in other optic neuropathies with mitochondrial dysfunction. This raises the possibility that defective expression of the IkB kinase complex-associated protein (IKAP) resulting from mutations in IKBKAP affects mitochondrial function in the metabolism-dependent retinal parvocellular ganglion cells in this condition.

Original languageEnglish (US)
Pages (from-to)238-244
Number of pages7
JournalJournal of neuropathology and experimental neurology
Issue number3
StatePublished - Mar 2017


  • Familial dysautonomia
  • Hereditary optic neuropathy
  • Histopathology
  • Optical coherence tomography
  • Retina
  • Riley-Day syndrome

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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