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Abstract #57220 Published in IGR 16-2
Myocilin modulates programmed cell death during retinal development
Koch MA; Rosenhammer B; Koschade SE; Braunger BM; Volz C; Jägle H; Tamm ERExperimental Eye Research 2014; 125: 41-52
Mutations in the myocilin gene (MYOC) are causative for 10% of cases with juvenile open-angle glaucoma and 3-4% of those with primary open-angle glaucoma. Myocilin is a secreted protein with relatively ill-defined matricellular properties. Despite its high expression in the eye, myocilin-deficient mice have originally been reported to have no obvious ocular phenotype. Here we revisited the ocular phenotype of myocilin-deficient mice and detected a higher number of neurons in their inner (INL) and outer (ONL) nuclear layers, as well as a higher number of retinal ganglion cells (RGC) and their axons. The increase in retinal neurons appears to be caused by a decrease in programmed developmental cell death, as apoptosis of retinal neurons between postnatal days 4 and 10 was found to be attenuated when compared to that of wildtype littermates. In contrast, when Myoc(-/-) mice were crossed with βB1-crystallin-MYOC mice with ectopic overexpression of myocilin in the eye, no differences in developmental apoptosis, RGC number and INL thickness were observed when compared to wildtype littermates. The amounts of the anti-apoptotic Bcl-2-like protein 1 (BCL2L1, Bcl-xL) and its mRNA were increased in retinae of Myoc(-/-) mice, while lower amounts of BCL2L1 and its mRNA were detected in mixed Myoc(-/-)/βB1-crystallin-MYOC mice. The structural differences between Myoc(-/-) mice and wildtype littermates did not result in functional differences as measured by electroretinography. Noteworthy though mixed Myoc(-/-)/βB1-crystallin-MYOC mice with ocular overexpression of myocilin had significant cone function deficits. Myocilin appears to modulate apoptotic death of retinal neurons likely by interacting with the intrinsic apoptotic pathway.
Full article
Classification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
3.6 Cellular biology (Part of: 3 Laboratory methods)
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
