Molecular genetics of primary open-angle glaucoma

Abstract

Glaucoma is a series of linked optic diseases resulting in progressive vision loss and total blindness due to the acquired loss of retinal ganglion cells. This harm to the optic nerve results in visual impairment and, ultimately, total blindness if left untreated. Primary open-angle glaucoma (POAG) is the most frequent variety within the large family of glaucoma. It is a multifaceted and heterogeneous condition with several environmental and genetic variables aiding in its etiology. By 2040, there will be 111.8 million glaucoma patients globally, with Asia and Africa accounting for the vast majority. The goal of this review is to elaborate on the role of genes (nuclear and mitochondrial) as well as their variants in the pathogenesis of POAG. PubMed and Google Scholar databases were searched online for papers until September 2022. Prevalence and inheritance patterns vary significantly across different ethnic and geographic populations. Numerous causative genetic loci may exist; however, only a few have been recognized and characterized. Further investigation into the genetic etiology of POAG is expected to uncover novel and intriguing causal genes, allowing for a more precise pathogenesis pattern of the disease.

Keywords: Cytochrome P450; genetics; myocilin; optineurin; primary open-angle glaucoma.

Figure 1

Flowchart depicting the summary of aqueous humor drainage including conventional and unconventional outflow

Figure 2

The structure of MYOC protein and common pathogenic mutations (in red). Source: Alphafold database

Figure 3

The structure of Cyp1b1 protein and common pathogenic mutations (in red). Source: Alphafold database

Figure 4

The structure of OPTN protein and common pathogenic mutations (in red). Source: Alphafold database

Figure 5

The structure of Wdr36 protein and common pathogenic mutations (in red). Source: Alphafold database

Figure 6

The structure of Tbk1 protein and common pathogenic mutations (in red). Source: Alphafold database

Figure 7

The structure of Ntf4 protein and common pathogenic mutations (in red). Source: Alphafold database

Figure 8

The structure of Foxc1 protein and common pathogenic mutations (in red). Source: Alphafold database

Figure 9

Genetic mechanisms lying behind the pathogenesis of POAG