Roots of Fuchs' dystrophy may be found in mitochondrial genes

By Laszlo Dosa

WASHINGTON, DC - A search for the genetic roots of Fuchs' dystrophy suggests a surprising role played by mitochondrial genes, reported John D. Gottsch MD at a Research to Prevent Blindness Foundation seminar.
"Although its precise aetiology is unknown, Fuchs' dystrophy is thought to be inherited and to involve a problem in one of several genes," Dr Gottsch noted.

The US researcher has investigated the inheritance patterns of Fuchs' dystrophy in large families and studied the molecular biological changes that occur in normal corneal endothelium of Fuchs' patients.

A new technique called serial analysis of gene expression (SAGE) was used to determine what genes are and are not working in normal endothelium compared to that affected by Fuchs' dystrophy.
SAGE found a profound decrease in most of the mitochondrial genes in the Fuchs' endothelium.

He explained that mitochondria are the major sources of cellular reactive oxygen species (ROS). Mitochondrial DNA is especially vulnerable to oxidative damage due to its close proximity to the inner mitochondrial membrane where electron transport systems generate ROS.

Dr Gottsch pointed to recent evidence indicating that oxidative DNA damage is a major cause of aging and has been associated with a number of age-related degenerative diseases.
Gradual oxidative mitochondrial DNA damage may occur over time in Fuchs' endothelial cells.

Dr Gottsch said a group of patients in large families was studied, looking at their affected and unaffected relatives, and found that the disease may not have simple autosomal dominant inheritance.

"There appear to be patients who are sporadically affected and do not have a history of inheritance. Some pedigrees show autosomal dominant inheritance and there is a definite preponderance of women in this disease.

"We are not sure why this occurs but clearly the majority of patients who present with signs of the disease and go on to surgery with penetrating keratoplasty (PK) are women," Dr Gottsch said.

Early in the disease, Fuchs' dystrophy symptoms, such of the swelling of the cornea, can be treated with ointments and drops which can be used as decongestants of the cornea and help restore vision.

However, as the disease progresses and the cornea thickens, corneal transplant has to be considered. When the disease is accompanied by a cataract, the standard procedure is to perform PK and cataract surgery at the same time.

Dr Gottsch has been looking at whether it may be feasible to do cataract surgery alone in patients whose Fuchs' dystrophy has not progressed. He found that these patients could retain their good vision by undergoing cataract surgery alone and not the graft.

"The way we make that distinction is by measuring the thickness of the cornea with a pachymeter. We believe the thickness of the cornea gives us a good idea of how well the endothelium is functioning and that if the pachymetry increases, that means the endothelium is not doing well.
"We have a cut-off level where we determine that the cornea would not remain clear after cataract surgery and that a transplant is necessary," he said.

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