Researchers from Jefferson Medical College, in collaboration with investigators from Belfast, Northern Ireland, and Kiel, Germany, have discovered genetic mututations that cause Meesmann's corneal dystrophy, a fragile eye disease characterized by a lifelong irritation of the cornea and a weak eye surface vulnerable to injuries and infection that prevents contact lens use. These findings appear in the June issue of Nature Genetics.
The Jefferson research team, led by Irwin McLean, PhD, Associate Professor of Dermatology and Director of the Epithelial Genetics Group, isolated, sequenced and studied the genes of members of two unrelated Irish families who exhibited Meesmann's corneal dystrophy. Researchers also studied a German family described in the 1930s by ophthalmologist Alois Meesmann, for whom the disease is named, and found that affected family members had defects in keratins K3 or K12, two proteins that play an important role in forming the cytoskeleton of cells forming the protective outer layer of the eye. This new information will allow for early diagnosis of infants born with Meesmann's corneal dystrophy as well as provide DNA-based prenatal testing for the disease.
Fifty percent of all children of parents affected with Meesmann's corneal dystrophy will develop the disorder, so prenatal testing via chorionic villi sampling (CVS), at an early stage of pregnancy, is beneficial for parents who have lived with the disorder.
It is estimated that one in 50,000 suffer from Meesmann's corneal dystrophy, but Dr. McLean and fellow researchers speculate that a larger number of people in the general population who cannot wear contact lenses, but do not have Meesmann's symptoms, may actually have mild gene mutations.
"The next stage of this research will be to isolate and sequence the genes of members of the population who cannot use contacts but lead normal everyday lives without experiencing the more serious effects of Meesmann's corneal dystrophy," said Dr. McLean. "It is our hypothesis that these people have mild gene mutations that share similarities with those who have Meesmann's."
Having identified the genetic mutations responsible for Meesmann's corneal dystrophy makes gene therapy a treatment on the horizon. "As gene therapies begin to rapidly develop, it is possible that in the future we will be able to use our new understanding of the cause of Meesmann's corneal dystrophy to correct the mutations," explained Dr. McLean.
This latest finding follows years of study by Jefferson researchers into various diseases causing fragility of skin and other tissues, such as epidermolysis bullosa (EB), a severe, inherited blistering skin disease. These discoveries and related studies of keratin diseases by the McLean group provided a solid foundation for the Meesmann's corneal dystrophy research.
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