Toward a Genetic Understanding of Glaucoma-Breakthroughs and Challenges from Studies of Exfoliation Glaucoma.

Abstract

Glaucoma is a complex group of diseases causing progressive degeneration of the optic nerve. Despite strong evidence of hereditary contributions to glaucoma, relatively few genetic mutations associated with glaucoma risk have thus far been identified. Glaucoma likely represents a complex genetic trait influenced by multiple loci and many confounding factors, increasing the challenge in identifying glaucoma’s hereditary basis. In this article, a brief history of the search for glaucoma-causing mutations is presented, highlighting recent breakthroughs that have identified lysyl oxidase-like 1 (LOXL1) as a major genetic risk factor contributing to exfoliative glaucoma. In considering challenges that remain ahead, our central tenet is that the search for glaucoma’s genetic elements will continue to require experimental ingenuity and synergistic approaches involving animal models that render the complexity of glaucoma more tractable.