Scientists Focus On 'Dwarf Eye' -- Genetic Finding May Have Implications For Farsightedness And Nearsightedness, Too

The researchers report that nanophthalmos, Greek for "dwarf eye," is arare, potentially blinding disorder caused by an alteration in a genecalled MFRP that helps control eye growth and regulates the organ'sshape and focus. The study is described in the July 5 issue of theProceedings of the National Academy of Sciences.

"The MFRP protein is only made in a tiny portion of the human eye, andit can alter eye refraction, or focus," said Olof Sundin, Ph.D.,assistant professor of ophthalmology at the Johns Hopkins School ofMedicine in the Wilmer Eye Institute. "We hope this protein holds thekey to unlocking not only nanophthalmos, but other forms offarsightedness and nearsightedness as well."

Hyperopia (farsightedness) and myopia (nearsightedness) -- the abilityto see only distant or near objects clearly, respectively -- stems fromthe complex growth of the human eye. All human eyes have a slightdegree of farsightedness at birth. As the child grows and gains morevisual experience, the eye adjusts its focus by growing, which changesthe distance between the lens and the retina, the light-detecting layerof cells at the back of the eye. Once the retina is the right distancefrom the lens for proper focus of images on the retina, a largelyunknown mechanism that uses visual experience causes the eye to stopgrowing.

Due to natural genetic mutations, some eyes continue to grow beyondthis point, causing nearsightedness. Other mutations cause the eye tostop growing too soon, causing farsightedness. In the case ofnanophthalmos, a mutation in MFRP completely wipes out the function ofthe protein coded for by the gene. In people with this condition, theretina is too close to the lens, but the lens and cornea, the eye'soutermost layer, are of normal size and shape.

"Eyes with nanophthalmos still work quite well, despite thesecomplications," said Sundin. "But the disease's secondary complicationslater in life, including glaucoma or detached retina, are far moresevere and can lead to complete blindness."

One such patient with nanophthalmos, an Amish-Mennonite womanwho was blind in one eye, came to the Wilmer Eye Institute in 1998 fortreatment. By reconstructing the woman's family tree, the researchersdiscovered that several living relatives also suffered fromnanophthalmos, and four deceased relatives had been part of the classicJohns Hopkins Bloomberg School of Public Health study in the 1970s thathelped define the disease as genetic.

In Sundin's study, the researchers examined the woman's DNA forpossible gene mutations causing nanophthalmos. According to Sundin,MFRP was a surprise candidate.

"Mutant MFRP was recently identified in mice as a cause of retinaldegeneration, not extreme farsightedness," he said. "However, a mouse'seyes do not adjust their focus through growth like human eyes do, soMFRP has a completely different