Year: 2010
Type: review
Abstract: Glaucoma, a leading cause of blindness worldwide, is characterized by progressive optic nerve damage, usually associated with intraocular pressure.Although the clinical progression of the disease is well defined, the molecular events responsible for glaucoma are currently poorly understood and current therapeutic strategies are not curative.This review summarizes the human genetics and genomic approaches that have shed light on the complex inheritance of glaucoma genes and the potential for gene-based and cellular therapies that this research makes possible. Genes identified using linkage approaches and multiplex familiesLarge multiplex families suitable for linkage analysis are typically affected by early-onset forms of glaucoma inherited as mendelian dominant or recessive traits.Most pedigrees affected by adultonset forms of glaucoma do not have the sufficient size and structure required for linkage studies, because the older age of onset typically limits these pedigrees to one and possibly two affected generations (7).To date, at least 29 genetic loci for various forms of glaucoma have been defined by linkage studies (8, 9), and 12 causative genes have been identified from these loci (Table 1).Genes and loci for different phenotypic forms of glaucoma are summarized below.Congenital glaucoma.The onset of congenital glaucoma is typically before 3 years of age and is characterized by very high IOP caused by abnormal development of the trabecular outflow pathways (10).This form of glaucoma is typically inherited as an autosomal recessive trait and is more common in countries and cultures that practice consanguinity.Linkage studies have identified four loci, GLC3A (2p22-p21) (11), GLC3B (1p36.2-p36.1)(12), GLC3C (14q24.3)(13), and GLC3D (14q24) (14), and two genes, CYP1B1, coding for cytochrome P450, family 1, subfamily B, polypeptide 1 at GLC3A (15), and more recently, LTBP2, coding for latent transforming growth factor-β-binding protein 2 at GLC3D (16, 17).Although known to cause congenital glaucoma for over a decade, the role of cytochrome P450 1B1 in glaucoma pathogenesis and development of the trabecular meshwork is not yet known but is hypothesized to participate in the metabolism of Conflict of interest:The authors have declared that no conflict of interest exists.
DOI: 10.1172/jci43085
Authors: Bao Jian Fan, Janey L. Wiggs
Institutions: Massachusetts Eye and Ear Infirmary, Harvard University
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2075562177