Mapping the Genetic Landscape of Nanophthalmos

Nanophthalmos is characterized by a small eye and severe farsightedness (high hyperopia). The condition can lead to a range of complications, from angle closure glaucoma to retinal and choroidal detachments.

How nanophthalmos develops is not completely understood. But an important piece of the puzzle was revealed in 2019, when Kellogg physician-scientist Lev Prasov, M.D., Ph.D. first linked the gene myelin regulatory factor (MYRF) to familial nanophthalmos. Using animal models, he also uncovered a role for MYRF in retinal pigment epithelial (RPE) development, finding that its disruption led to retinal degeneration in mice.

Dr. Prasov has been awarded a Mentored Clinical Scientist Research Career Development (K-08) award from the National Institutes of Health to build on that work.

“In a study of families with nanophthalmos, we found that known genes, including MYRF, were implicated in only 20 percent of cases,” says Dr. Prasov. “But we hypothesize that the other 80 percent of cases may be explained by other, yet to be identified genes, that may be targets or interacting partners of MYRF, whose primary function is to control expression of other genes.”

This grant will be used to catalog the genetic determinants of nanophthalmos and high hyperopia, including describing the mechanism by which MYRF disrupts RPE structure and function.

A team of mentors and collaborators led by Dr. Sally Camper will support Dr. Prasov, providing instruction and supervision in developmental and medical genetics, RPE biology, genomics and bioinformatics.

“My hope is that a better understanding the genetic and molecular mechanisms of small eyes and hyperopia will point to new therapeutic targets for these diseases,” he says. “The findings may also shed useful light on the other end of the spectrum, namely, myopia that results from too large an eye.”

Dr. Prasov’s K-08 Mentor and Advisor Team:

Sally Camper, Ph.D., Professor of Internal Medicine

Jun Li, Ph.D., Professor of Human Genetics

David Zacks, M.D., Ph.D., Professor of Ophthalmology and Visual Sciences

Robert B. Hufnagel, M.D., Ph.D., Director, Ophthalmic Genomics Laboratory