"Eyes with nanophthalmos still work quite well, despite these complications," said Sundin. "But the disease's secondary complications later in life, including glaucoma or detached retina, are far more severe and can lead to complete blindness."
One such patient with nanophthalmos, an Amish-Mennonite woman who was blind in one eye, came to the Wilmer Eye Institute in 1998 for treatment. By reconstructing the woman's family tree, the researchers discovered that several living relatives also suffered from nanophthalmos, and four deceased relatives had been part of the classic Johns Hopkins Bloomberg School of Public Health study in the 1970s that helped define the disease as genetic.
In Sundin's study, the researchers examined the woman's DNA for possible gene mutations causing nanophthalmos. According to Sundin, MFRP was a surprise candidate.
"Mutant MFRP was recently identified in mice as a cause of retinal degeneration, not extreme farsightedness," he said. "However, a mouse's eyes do not adjust their focus through growth like human eyes do, so MFRP has a completely different function in mice and was not assumed to alter eye refraction in humans."
The research team successfully mapped the MFRP gene mutation in humans and discovered that the protein was completely missing from nanophthalmos patients.
In a normal human eye, the MFRP protein is located on the surface of the retinal pigment epithelium (RPE), which is located beneath the retina and helps maintain photoreceptors, the eye's light-detecting cells. Blindness occurs when these cells die after detachment of the retina from the RPE.
Beneath the RPE are two layers of structural tissue that give the eye its shape. During childhood, these tissues stretch, like a balloon, as the eye grows. "The RPE is believed to be the key link in signaling the
Source:Johns Hopkins Medical Institutions