February 18, 2021

Genetic clues in eye birth defect

Sabine Fuhrmann and colleagues have discovered a novel underlying cause of coloboma — a birth defect that causes missing tissue in the eye and accounts for up to 10% of childhood blindness.

by Leigh MacMillan

Uveal coloboma can affect the iris — the colored part of the eye — giving it a keyhole appearance. (iStock)

Uveal coloboma — a birth defect that causes a malformation of the eye — accounts for up to 10% of childhood blindness. Coloboma results from a defective fusion of the optic fissure during eye development. 

Mutations in the gene encoding Neurofibromin 2 (NF2) can cause eye abnormalities in humans, including coloboma, but the precise role of NF2 in optic fissure closure is not clear. 

Sabine Fuhrmann, PhD, and colleagues used genetic strategies to inactivate the gene for NF2 in the developing mouse eye. They discovered that eyes lacking NF2 had increased proliferation of retinal pigmented epithelial cells in the optic fissure region. The cells failed to transition to a cuboidal shape, resulting in insufficient alignment of the optic fissure margins, failure to fuse and persistent coloboma. 

The findings, reported in the journal Human Molecular Genetics, indicate that loss of NF2 function and expansion of the retinal pigmented epithelium is a novel underlying cause of coloboma.

This research was supported by the National Institutes of Health (grants EY024373, HD007502, EY008126) and Research to Prevent Blindness Inc.