Koch, Marcus A. and Rosenhammer, Bernd and Koschade, Sebastian E. and Braunger, Barbara M. and Volz, Cornelia and Jaegle, Herbert and Tamm, Ernst R. (2014) Myocilin modulates programmed cell death during retinal development. EXPERIMENTAL EYE RESEARCH, 125. pp. 41-52. ISSN 0014-4835, 1096-0007
Full text not available from this repository. (Request a copy)Abstract
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 beta B1-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 (-/-)/beta B1-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(-/-)/beta B1-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. (C) 2014 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRABECULAR MESHWORK CELLS; OPEN-ANGLE GLAUCOMA; TRANSGENIC MICE; AQUEOUS-HUMOR; NERVOUS-SYSTEM; GANGLION-CELLS; EXTRACELLULAR-MATRIX; OLFACTOMEDIN DOMAIN; SIGNALING PATHWAY; WNT/BETA-CATENIN; apoptosis; retinal ganglion cells; optic nerve; myocilin; transgenic animals |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie > Prof. Dr. Ernst Tamm |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Sep 2019 13:13 |
| Last Modified: | 04 Sep 2019 13:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9815 |
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