Genetic clues to glaucoma's secrets. The L Edward Jackson Memorial Lecture. Part 2

Abstract

Major advances in the medical and surgical treatment of glaucoma have occurred since the first Edward Jackson Memorial lecture was delivered 50 years ago. Collaborative clinical trials under the sponsorship of the National Eye Institute are adding to our knowledge about which patients to treat and how to treat them. Despite these clinical advances, an understanding of the pathophysiologic and biochemical mechanisms that cause the disease remain unknown. The 40th anniversary of the discovery of the DNA double helix provides a springboard for a historical perspective on the heritability of glaucoma. A large pedigree is presented of a family with autosomal dominantly inherited primary open-angle glaucoma of juvenile onset. This is the second family with this clinical entity to show genetic linkage to the long arm of chromosome 1. Other forms of primary open-angle glaucoma with adult onset are presented wherein the inheritance pattern suggests autosomal recessive transmission. Thus far, linkage analysis does not suggest a genetic relationship to the autosomal dominant juvenile-onset pedigree that links to the long arm of chromosome 1. It is hoped that an emphasis on clinical and molecular genetic studies of glaucoma will yield protein defects that can be targeted for treatment. It is emphasized that the clinical ophthalmologist can participate in this important work by finding families with glaucoma and collaborating with individuals capable of extracting DNA, manipulating it, and performing genetic linkage and positional cloning studies.