Results suggested that genetic variation in five of the candidate genes (RDX, SNX16, OPA1, SOD2 and CYP1B1) is unlikely to confer major risk to develop normal tension glaucoma in the German population.
Interestingly, patients who carry the gain-of-function mutation of the pro-inflammatory gene TBK1 - tumor necrosis factor (TNF) receptor associated factor NF-κB activator (TANK) binding kinase 1 - are at increased risk to develop NTG.
We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)--POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)--and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians.
The association of the allelic variation (Met98Lys) in the OPTN gene and the prevalence of POAG and NTG in unrelated Japanese patients suggest that they are involved in the pathogenesis of POAG and NTG.
In this study, subjects with glaucoma who had the OPTNE50K mutation were found to have NTG that appeared to be more severe than that in a control group of subjects with NTG without this mutation.
Together, these data link the duplication of genes on chromosome 12q14 with familial NTG and suggest that an extra copy of the encompassed TBK1 gene is likely responsible for these cases of glaucoma.
We have refined the previously reported association between OPA1 sequence changes and NTG by identifying a specific CC genotype at position +32 in IVS8 of the OPA1 gene that acts as a marker for NTG.
In this manuscript, we focus on the OPTN E50K mutation, the most common mutation for NTG, to describe the molecular mechanism of NTG by expressing a mutant Optn gene in cells and genetically modified mice.
Additionally, the GCIPL thinning rates were compared between normal-baseline-IOP OAG (normal-tension glaucoma [NTG]) and high-baseline-IOP OAG (high-tension glaucoma [HTG]) eyes.
Further, the TBK1 copy number variation segregated with normal-tension glaucoma in the family members of the probands, showing an autosomal dominant pattern of inheritance.
To determine a chemical agent that can reduce the aggregation of optineurin (OPTN) in cells differentiated from induced pluripotent stem cells obtained from a patient with normal-tension glaucoma (NTG) caused by an E50K mutation in the OPTN gene (OPTNE50K-NTG).
The frequency of the OPTN M98K mutation in an additional 120 patients (70 HTG and 50 normal tension glaucoma [NTG]) was analyzed by restriction enzyme digestion.