Interaction between two glaucoma genes, optineurin and myocilin.

Myocilin (MYOC) and optineurin (OPTN) are two genes linked to glaucoma, a major blinding disease. To investigate the possible molecular interactions between MYOC and OPTN genes, we over-expressed MYOC and examined its effect on the level of endogenous OPTN in human trabecular meshwork (TM) cells and vice versa. We noted that over-expressing MYOC did not affect the OPTN level, whereas OPTN over-expression induced an up-regulation of the endogenous MYOC. This induction was also observed in other ocular and non-ocular cell types including PC12 cells. The endogenous levels of both OPTN and MYOC genes were in addition found increased when PC12 cells underwent differentiation upon treatment with nerve growth factor (NGF). Over-expression of OPTN resulted in prolonged turnover rate of MYOC mRNA but had little effect on the promoter activity of the MYOC gene. The over-expressed OPTN was localized in the cytoplasm, not translocated into the nucleus. These results indicate that interaction exists between OPTN and MYOC genes. Regulation of MYOC expression by OPTN is achieved primarily through control of the mRNA stability.