The cell and molecular biology of complex forms of glaucoma: updates on genetic, environmental, and epigenetic risk factors.

Glaucoma is a clinically and genetically heterogeneous disease. First-degree relatives of primary open-angle glaucoma (POAG) patients have a disease prevalence that is between 4 and 10 times higher than that of the general population, and there is a higher disease concordance in monozygotic twins than in dizygotic twins. These studies indicate the significant heritability of POAG; however, a simple mode of inheritance is not likely and cannot be assumed in genetic studies designed to identify POAG susceptibility genes. POAG is also complex clinically. The relationship between intraocular pressure (IOP) elevation and retinal ganglion cell degeneration is not simple, as many individuals have IOP elevation without optic nerve damage, and in some individuals, optic nerve degeneration develops without elevated IOP. Recent studies have shown that POAG-related clinical features, including optic nerve parameters, central corneal thickness, and IOP, are influenced by different sets of genes. Genetic and environmental risk factors and epigenetics are thought to influence complex traits such as POAG, normal tension glaucoma (NTG) and exfoliation syndrome–related glaucoma (Fig. 1).