Not all Inherited Mitochondrial Diseases Produce an Optic Neuropathy

Abstract

Purpose: : Some inherited diseases of mitochondrial dysfunction such as Leber Hereditary Optic Neuropathy and Dominant Optic Atrophy produce blindness or at least a subclinical optic neuropathy that produces a characteristic pattern of optic atrophy. In this study, we describe the histopathological features in postmortem optic nerves from two patients with two different mitochondrial disorders, Mitochondrial Myopathy, Encephalopathy and Lactic Acidosis and Stroke Syndrome (MELAS) and Kearns Sayre Syndrome (KSS) who presented with visual loss.

Methods: : Right retrobulbar optic nerves were obtained at autopsy from a twenty-seven year old male patient with KSS and a forty-five year old male with MELAS who both died of complications from their diseases. Age-matched controls were obtained from the Lions Eye Bank of Oregon. Tissues were fixed in 10 % neutral buffered formalin (NBF), dissected into cross-sectional profiles and embedded into paraffin. Tissue blocks were sectioned at 5 microns and immunostained for neurofilament (NF) protein using an indirect immunoperoxidase method with diaminobenzadine as the chromagen. Stained axons within the bundles (fascicles) of each optic nerve were examined in five quadrants or "zones"; superior, inferior, nasal, temporal, and central on a Zeiss Axioskop bright field microscope. Images were captured with a Spot II digital camera at various magnifications.

Results: : The control optic nerves demonstrated a normal homogenous staining pattern reflecting intact bundles of axons in all quadrants. Both optic nerves from both patients with mitochondrial disorders showed normal optic nerves consisting of about one thousand bundles each containing about one thousand retinofugal fibers. Neither the patient with MELAS nor KSS showed focal or diffuse areas of degeneration or optic atrophy.

Conclusions: : Notwithstanding the underlying mitochondrial disorders, the integrity of fibers in both optic nerves from the patients with MELAS and KSS appeared entirely intact. Unlike LHON or DOA or even Friedreich’s Ataxia, these mitochondrial disorders show no evidence of even a subclinical optic neuropathy.

Keywords: neuro-ophthalmology: optic nerve • mitochondria • immunohistochemistry