The pattern of retinal ganglion cell dysfunction in Leber hereditary optic neuropathy

A Majander,A.G Robson,C João,G.E Holder,P.F Chinnery,A.T Moore,M Votruba,A Stockman,P Yu-Wai-Man

doi:10.1016/j.mito.2017.07.006

Abstract

Leber inherited optic neuropathy (LHON) is characterized by subacute bilateral loss of central vision due to dysfunction and loss of retinal ganglion cells (RGCs). Comprehensive visual electrophysiological investigations (including pattern reversal visual evoked potentials, pattern electroretinography and the photopic negative response) performed on 13 patients with acute and chronic LHON indicate early impairment of RGC cell body function and severe axonal dysfunction. Temporal, spatial and chromatic psychophysical tests performed on 7 patients with acute LHON and 4 patients with chronic LHON suggest severe involvement or loss of the midget, parasol and bistratified RGCs associated with all three principal visual pathways.

Highlights

Leber hereditary optic neuropathy (LHON) (OMIM 535000) is a primary mitochondrial DNA disorder that presents with bilateral subacute loss of central vision (Nikoskelainen et al, 1996; YuWai-Man and Chinnery, 2013; Yu-Wai-Man et al, 2014)
Macular SD-optical coherence tomography (OCT) revealed selective loss of the GCL-inner plexiform layer (IPL) complex thickness (50% of the normal) within the first few months of disease onset in LHON as shown in the Supplementary Table S1 and Fig. 1
Our comprehensive electrophysiological and psychophysical study of patients with acute and chronic LHON highlights the marked extent of retinal ganglion cells (RGCs) dysfunction in this classical mitochondrial optic neuropathy

Summary

Introduction

Leber hereditary optic neuropathy (LHON) (OMIM 535000) is a primary mitochondrial DNA (mtDNA) disorder that presents with bilateral subacute loss of central vision (Nikoskelainen et al, 1996; YuWai-Man and Chinnery, 2013; Yu-Wai-Man et al, 2014). The histopathological observation of loss of the small calibre axons that constitute the papillomacular bundle was originally observed on histopathological sections of post mortem optic nerve samples obtained several decades after disease onset (Sadun et al, 1994; Kerrison et al, 1995; Sadun et al, 2000). In vivo studies involving highresolution optical coherence tomography (OCT) have revealed a major loss of the temporal peripapillary nerve fiber (RNFL) and macular RGC layers within 3 months of disease onset.

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