Molecular genetics is revolutionizing our understanding of ophthalmic disease

Purpose: To inform ophthalmologists of the extraordinary progress in molecular genetics that is revolutionizing our understanding of ophthalmic disease and of the crucial role of the clinician in facilitating genetic discovery.Method: Review of relevant articles.Results: Genes for many mendelian-inherited eye diseases have been localized and some identified using three general approaches: positional cloning, which requires no knowledge of underlying pathophysiology; a candidate gene approach, which examines genes based on their likely function; and a positional candidate approach, which uses map location as well as candidate genes in the linked region to isolate a gene. In positional cloning, once linkage is obtained, the gene can eventually be isolated, cloned, and sequenced and mutations identified. Techniques in molecular biology and other disciplines can then be used to unravel the pathophysiology of a disease.Conclusions: Molecular genetics is advancing our understanding of the classification and pathophysiology of ophthalmic diseases. The present classification system, based largely on clinical description of disease, is being replaced with a more rational classification based on genetic causes. Future research will determine the function of known genes and identify susceptibility loci for complex diseases such as chronic open-angle glaucoma and age-related macular degeneration. More specific diagnostic, therapeutic, and preventive strategies for ophthalmic disease will be developed. Clinicians play a crucial role by inquiring about the family history of all patients, identifying individuals and families with a genetic trait, and, when appropriate, referring them for further investigation