Abstract
Purpose :
Trabecular meshwork inducible glucocorticoid receptor (TIGR), also known as myocilin (MYOCgene, was the first gene to be identified and linked to both juvenile open angle glaucoma (JOAG) and POAG. The function of myocilin in POAG development remains unknown, but it has been suggested that mutations in the MYOC gene and the aggregation of mutant myocilin in the ER of TM may cause ER stress, resulting in a reduced outflow of aqueous humor and an increase in IOP. Therefore, we decide to Determine the possible relationship between melting temperature of mutated myocilin and the age at glaucoma diagnosis of patients.
Methods :
Guided by the data present in myocilin.com, all publications before April 2018 on the topic of MYOC mutations in glaucoma are included. Because experimentally determined melting temperatures of 20 mutations are available, information on age at glaucoma diagnosis were collected for patients who carry one of those 20 MYOC mutations. Total of 40 publications were identified. Each article was reviewed for MYOC mutation and age at diagnosis of glaucoma patients. 20 (50%) articles met the inclusion criterion: at least one glaucoma patient with MYOC mutation and information on age at glaucoma diagnosis.
Primary study outcome was the age at glaucoma diagnosis of patients with MYOC mutations. The prognostic factor was melting temperature of mutated myocilin. The hypothesis is a positive correlation between melting temperature and age at glaucoma diagnosis; Pearson correlation coefficient was calculated between these two measures. Scatter plot with a fitted linear line was generated to illustrate the correlation visually. If individual age at diagnosis was unavailable, two statistical methods were used to impute individual age.
Results :
458 patients from 20 studies were included. 283 patients from 18 studies had known the age at glaucoma diagnosis and melting temperature for each patient, while 175 patients from 9 studies had unknown individual age values. A statistically significant (and similar) correlation was present, ranging from 0.36 to 0.38, between age and melting temperature based on various assumptions for age.
Conclusions :
A weak to moderate but statistically significant correlation was found. Therefore, other possible moderating variables such as environments and genetic backgrounds may also play a role.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.