Optic neuropathies: The tip of the neurodegeneration iceberg

Valerio Carelli, Chiara La Morgia, Fred N. Ross-Cisneros, Alfredo A. Sadun

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

The optic nerve and the cells that give origin to its 1.2 million axons, the retinal ganglion cells (RGCs), are particularly vulnerable to neurodegeneration related to mitochondrial dysfunction. Optic neuropathies may range from non-syndromic genetic entities, to rare syndromic multisystem diseases with optic atrophy such as mitochondrial encephalomyopathies, to age-related neurodegenerative diseases such as Alzheimer's and Parkinson's disease where optic nerve involvement has, until recently, been a relatively overlooked feature. New tools are available to thoroughly investigate optic nerve function, allowing unparalleled access to this part of the central nervous system. Understanding the molecular pathophysiology of RGC neurodegeneration and optic atrophy, is key to broadly understanding the pathogenesis of neurodegenerative disorders, for monitoring their progression in describing the natural history, and ultimately as outcome measures to evaluate therapies. In this review, the different layers, from molecular to anatomical, that may contribute to RGC neurodegeneration and optic atrophy are tackled in an integrated way, considering all relevant players. These include RGC dendrites, cell bodies and axons, the unmyelinated retinal nerve fiber layer and the myelinated post-laminar axons, as well as olygodendrocytes and astrocytes, looked for unconventional functions. Dysfunctional mitochondrial dynamics, transport, homeostatic control of mitobiogenesis and mitophagic removal, as well as specific propensity to apoptosis may target differently cell types and anatomical settings. Ultimately, we can envisage new investigative approaches and therapeutic options that will speed the early diagnosis of neurodegenerative diseases and their cure.

Original languageEnglish
Pages (from-to)R139-R150
JournalHuman Molecular Genetics
Volume26
Issue numberR2
DOIs
Publication statusPublished - Oct 1 2017

Fingerprint

Ice Cover
Optic Nerve Diseases
Retinal Ganglion Cells
Optic Atrophy
Optic Nerve
Neurodegenerative Diseases
Axons
Mitochondrial Encephalomyopathies
Mitochondrial Dynamics
Unmyelinated Nerve Fibers
Dendrites
Natural History
Astrocytes
Parkinson Disease
Early Diagnosis
Alzheimer Disease
Central Nervous System
Outcome Assessment (Health Care)
Apoptosis
Neurons

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Optic neuropathies : The tip of the neurodegeneration iceberg. / Carelli, Valerio; Morgia, Chiara La; Ross-Cisneros, Fred N.; Sadun, Alfredo A.

In: Human Molecular Genetics, Vol. 26, No. R2, 01.10.2017, p. R139-R150.

Research output: Contribution to journalReview article

Carelli, Valerio ; Morgia, Chiara La ; Ross-Cisneros, Fred N. ; Sadun, Alfredo A. / Optic neuropathies : The tip of the neurodegeneration iceberg. In: Human Molecular Genetics. 2017 ; Vol. 26, No. R2. pp. R139-R150.
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