Leber's Hereditary Optic Neuropathy
Volunteer Study Program

LHON Frequently Asked Questions

Study Participation Information


Leber's Hereditary Optic Neuropathy (LHON), first recognized almost 150 years ago by Von Graefe and Leber, is a familial condition of rapid loss of central vision. In 1988, Wallace and coworkers first identified a mutation in the mitochondrial DNA responsible for LHON disease. Genetic testing has greatly improved our ability to diagnose LHON, however, LHON remains poorly understood as a mitochondrial diseases.

Unsolved questions include the specific optic nerve involvement, the delayed onset and incomplete penetrance, the prevalence in males and the associations of LHON with other central nervous system (CNS) disorders. Visual failure in LHON predominantly affects males in their twenties and, less frequently, females at a slightly later age. The age of onset is now recognized to vary broadly, including pediatric as well as late-onset cases.Leber's Hereditary Optic Neuropathy Volunteer Study Program

The stereotyped presentation of LHON comprises rapid loss of central vision in one eye, usually described as painless blurring with fading of colors (dyschromatopsia), followed by similar involvement of the other eye, with a delay varying from days to months, rarely years. A few unilateral cases have also been reported. Typically, visual acuity deteriorates over a period of days to weeks, reaching stable residual values at or below 20/400 after a few months. The evolution of the visual field defect is usually represented by an enlargement of the blind spot that progressively involves the central vision in the form of a large centro-cecal absolute scotoma.

Fundus examination during the acute/subacute stage in most cases reveals characteristic changes that include1) circumpapillary telangiectatic microangiopathy2) swelling of the nerve fiber layer around the disc (pseudoedema)3) absence of leakage on fluorescein angiography (in contrast to true edema).

Axonal loss in the papillomacular bundle leads, over weeks, to temporal atrophy of the optic disc. Similar but slower changes also involve the nasal side and eventually the optic disc turns pale. Optic atrophy, with permanent severe loss of central vision but relative preservation of pupillary light responses, represents the usual endpoint of the disease.

Leber's Hereditary Optic Neuropathy Volunteer Study Program Leber's Hereditary Optic Neuropathy Volunteer Study Program


The overall objective of the proposed research is to test the hypothesis that near-infrared (NIR) light emitting diode (LED) photobiomodulation will stimulate mitochondrial function, attenuate oxidative stress and improve cell survival in a cellular model of Leber's Hereditary Optic Neuropathy (LHON).

Leber's Hereditary Optic Neuropathy Volunteer Study Program Leber's Hereditary Optic Neuropathy Volunteer Study Program


Current Status

Leber's Hereditary Optic Neuropathy Volunteer Study Program

Our laboratory has recently shown that photobiomodulation by light in the red to near-infrared range (670-880 nm) using light-emitting diode (LED) arrays stimulates mitochondrial function, augments antioxidant protein synthesis and protects against mitochondrial toxins (8, 20, 21) in vitro and in vivo. Importantly, we have recently obtained preliminary evidence that a brief course of NIR-LED treatment produced marked improvement in peripheral vision in affected LHON patients in Colatina, Brazil (ARVO abstract). Based on these observations we propose to examine the efficacy and molecular mechanism of cytoprotection of NIR LED photobiomodulation in a cellular model of Leber's Hereditary Optic Neuropathy (LHON).


Basic Science and Clinical Significance

Mitochondrial dysfunction and oxidative damage to biological molecules in the retina and optic nerve is known to contribute to the pathogenesis of LHON and has been postulated to contribute to retinal aging and age related retinal diseases. From a basic science perspective, successful completion of the studies outlined in this proposal will improve our understanding of the pathogenesis of LHON and will provide valuable insight into the role of mitochondrial function in retinal aging and retinal disease. From a clinical perspective, information obtained from these studies will determine if photobiomodulation with red to near infrared light augments mitochondrial function and cell survival pathways in an in vitro model of an important clinical disease. This may of may lead to the development of NIR-LED as a innovative, non-invasive, drug-free therapeutic approach for the treatment of retinal diseases including Leber's hereditary optic neuropathy age-related macular degeneration, glaucoma and diabetic retinopathy.

Leber's Hereditary Optic Neuropathy Volunteer Study Program