Genetic Insights and Epidemiological Models in Understanding Primary Open Angle Glaucoma
Benedict C. Umezurike *
Department of Optometry, Faculty of Allied Health Science, Gregory University, Uturu. Abia State Nigeria.
Moses O. Akhimien
State Team Lead, African Field Epidemiology Network, AFENET/NSTOP, Gusau Field Office, Commissioners quarter, Gusau, Zamfara State, Nigeria
Chidinma Chukwuka
Department of Optometry, Faculty of Allied Health Science, Gregory University, Uturu. Abia State Nigeria.
Thaddaeus C. Ejike
Department of Optometry, Faculty of Allied Health Science, Gregory University, Uturu. Abia State Nigeria.
Louis Ugwulor
Department of Public Health, Faculty of Allied Health Science, Gregory University, Uturu. Abia State Nigeria.
Bright Ajoku
Department of Public Health, Faculty of Allied Health Science, Gregory University, Uturu. Abia State Nigeria.
Solomon N. Ijioma
Department of Human Physiology, Micheal Okpara University of Agriculture, Umudike, Umuahia, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
Primary open-angle glaucoma (POAG) is a multifactorial chronic optic neuropathy with significant genetic heterogeneity. The pathogenesis of POAG involves an imbalance between the production and drainage of aqueous humor (AH). Genetic theories suggest that transgenic mice demonstrating the GLU50LYS mutation in optineurin (OPTN) experience retinal ganglion cell apoptosis, while mutant myocilin (MYOC) proteins induce endoplasmic reticulum (ER) stress, leading to an unfolded protein response (UPR) and subsequent apoptosis of trabecular meshwork cells (TMC). Furthermore, the interaction between MYOC and mitochondria in the trabecular meshwork (TM) and astrocytes may lead to mitochondrial membrane depolarization and calcium channel dysregulation, contributing to POAG. Overexpression of MYOC variants (P370L, Q368X) is also implicated, as are epigenetic modifications and signaling pathways such as histone and DNA modification. POAG has been associated with autosomal dominant inheritance, with mutations in MYOC and OPTN being prominent causative factors, although many cases involve multiple genetic loci. Currently, over 20 genetic loci have been linked to POAG, with 14 chromosomal loci (GLC1A to GLC1N) identified, 5 of which contribute to juvenile-onset open-angle glaucoma (JOAG). Of these loci, MYOC, OPTN, WD repeat domain 36 (WDR36), and neurotrophin-4 (NTF4) are the most studied causative genes. The ongoing study of molecular genetics offers potential pathways for future therapeutic advances in the treatment of POAG.
Keywords: Primary open-angle glaucoma, mutation, gene locus, genetic mapping, mendelian inheritance, gene penetrance