Eyeworld

EW CORNEA 42 June 2017 by Lauren Lipuma EyeWorld Contributing Writer LAMC1 genetic variants confer a sig- nificantly higher risk of developing Fuchs' among women, while TCF4 variants confer a greater risk among men. However, these genes' precise role in mediating sex-specific risk is still unclear, Dr. Afshari said. The researchers also used immunohistochemistry to look at expression of proteins associated with these genes in Fuchs' patients who underwent Descemet's strip- ping endothelial keratoplasty (DSEK) or Descemet's membrane endo- thelial keratoplasty (DMEK). They found proteins associated with the three genes were present in DSEK and DMEK patients, suggesting the proteins play essential roles in maintaining the corneal endothe- lium, such as regulating cell-to-cell contact and maintaining the base- ment membrane and tissue integrity, according to the study. The authors suspect all three genes regulate fluid transport within the cornea, with ATP1B1 having the most obvious role, as it encodes a subunit of the sodium-potassium plasma membrane pump, according to the study. The study provides a deeper un- derstanding of the underlying mech- anism behind Fuchs' dystrophy, Dr. Afshari said. Because Fuchs' is hered- itary, the study results could lead to the development of new treatments for Fuchs' and earlier detection of the disease with future molecular diagnostic tools, she added. "It allows a way to diagnose this disease with 78% accuracy or so," said George McKie, PhD, director of the cornea research program, National Eye Institute, Bethesda, Maryland, who was not connected to the study. "This allows someone with a family history to go in and say, 'Do I have this? Do I need to be concerned about this?' Hopefully be- cause they know what the causative genes are, in the future they'll know what the genes did and develop individualized treatment." EW Reference 1. Afshari NA, et al. Genome-wide associa- tion study identifies three novel loci in Fuchs endothelial corneal dystrophy. Nat Commun. 2017 Mar 30;8:14898. Editors' note: Drs. Afshari and McKie have no financial interests related to their comments. Contact information Afshari: naafshari@ucsd.edu McKie: balintfyj@nei.nih.gov sight-threating disease, in addition to the gene TCF4, a previously known genetic risk factor. A multinational team of 16 re- search groups conducted a genome- wide association study of 2,075 eyes with Fuchs' and 3,342 control eyes. Together the four genetic loci de- scribed by the study predict the risk of an individual developing Fuchs' dystrophy with an accuracy of about 78%, said Natalie Afshari, MD, chief of cornea and refractive sur- gery, Shiley Eye Institute, University of California, La Jolla, California, and lead author of the new study published in Nature Communications. "There are no real clinical screening tools before a patient develops the disease, so this would be a significant advancement for the development of molecular diagnos- tics," Dr. Afshari told EyeWorld. The study also discovered the first known sex-specific genetic as- sociation with Fuchs' dystrophy, Dr. Afshari said. Ophthalmologists pre- viously knew Fuchs' was more com- mon in women than men but could not recognize a genetic reason for the disparity. The new study shows The results of the largest Fuchs' dystrophy study to date could prompt the development of individualized treatment for the corneal disease T hree genes responsible for water transport, basement membrane maintenance, cell-to-cell interactions, and tissue integrity are associated with the development of Fuchs' dystrophy, the most common disorder requiring corneal transplan- tation, a new study finds. The largest-ever study of Fuchs' dystrophy has discovered that genes KANK4, LAMC1, and ATP1B1 are associated with development of the Researchers discover three new genetic risk factors for Fuchs' dystrophy

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