title: Complex genetic mechanisms in glaucoma: an overview.
abstract: Glaucomas comprise a group of hereditary optic neuropathies characterized by progressive and irreversible visual field loss and damage to the optic nerve head. It is a complex disease with multiple molecular mechanisms underlying its pathogenesis. Genetic heterogeneity is the hallmark of all glaucomas and multiple chromosomal loci have been linked to the disease, but only a few genes have been characterized, viz. myocilin (MYOC), optineurin (OPTN), WDR36 and neurotrophin-4 (NTF4) in primary open angle glaucoma (POAG) and CYP1B1 and LTBP2 in congenital and developmental glaucomas. Case-control-based association studies on candidate genes involved in different stages of glaucoma pathophysiology have indicated a very limited involvement. The complex mechanisms leading to glaucoma pathogenesis indicate that it could be attributed to multiple genes with varying magnitudes of effect. In this review, we provide an appraisal of the various efforts in unraveling the molecular mystery in glaucoma and also some future directions based on the available scientific knowledge and technological developments.
authors.affiliation: Kallam Anji Reddy Molecular Genetics Laboratory, Prof Brien Holden Eye Research Centre, LV Prasad Eye Institute, Hyderabad, India.
authors.forename: Kollu N
authors.initials: KN
authors.lastname: Rao
authors.forename: Srujana
authors.initials: S
authors.lastname: Nagireddy
authors.forename: Subhabrata
authors.initials: S
authors.lastname: Chakrabarti
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001323:Autoantibodies / Q000276:immunology; D018797:Cell Cycle Proteins; D016923:Cell Death; D002874:Chromosome Mapping; D003165:Complement System Proteins / Q000276:immunology; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D004843:Epistasis, Genetic; D005136:Eye Proteins / Q000235:genetics; D015870:Gene Expression; D018740:Genetic Heterogeneity; D015894:Genome, Human; D005901:Glaucoma / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D005902:Glaucoma, Open-Angle / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D026901:Membrane Transport Proteins; D009414:Nerve Growth Factors / Q000235:genetics; D009798:Ocular Hypertension / Q000209:etiology; D012165:Retinal Ganglion Cells; D012307:Risk Factors; D035582:Transcription Factor TFIIIA / Q000235:genetics; D000099179:Myocilin
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D001323:Autoantibodies; D018797:Cell Cycle Proteins; D003165:Complement System Proteins; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D009414:Nerve Growth Factors; D035582:Transcription Factor TFIIIA; D000099179:Myocilin; C409460:OPTN protein, human; C502341:WDR36 protein, human; C585496:CYP1B1 protein, human; C073922:neurotrophin 4