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Ribonuclease 5 coordinates signals for the regulation of intraocular pressure and inhibits neural apoptosis as a novel multi-functional anti-glaucomatous strategy.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2016 Feb; Vol. 1862 (2), pp. 145-54. Date of Electronic Publication: 2015 Nov 12. - Publication Year :
- 2016
-
Abstract
- Glaucoma is a vision-threatening disorder characterized by progressive death of retinal ganglion cells (RGCs), although little is known about therapeutic milestones. Due to its complex and multifactorial pathogenesis, multipronged therapeutic approach is needed. Angiogenin (ANG), now called ribonuclease (RNase) 5, has been previously known as angiogenic factor and more recently its biologic activity is extended to promoting cell survival via its ribonucleolytic activity. Here, we revealed the defect of ANG in human glaucomatous trabecular meshwork (TM) cells and identified novel multiple functions of ANG as an anti-glaucomatous strategy. ANG was highly expressed in normal eyes and normal TM cells compared to glaucomatous TM cells. ANG induced intraocular pressure (IOP) lowering in rat models of both normal and elevated IOP, and as a possible mechanism, activated Akt-mediated signals for nitric oxide (NO) production, an important regulator of IOP in glaucomatous TM cell. Moreover, we demonstrated ANG-induced production of matrix metalloproteinase (MMP)-1 and -3 and rho-kinase inhibition for TM remodeling. For anti-glaucomatous defense optimization, ANG not only elicited immune-modulative pathways via indolamine 2,3-dioxygenase (IDO) activation in TM cells and suppression of Jurkat T cells, but also rescued neural stem cells (NSCs) from apoptosis induced by glaucomatous stress. These results demonstrate that novel multi-functional effects of ANG may have benefits against glaucoma in ocular tissues.<br /> (Copyright © 2015. Published by Elsevier B.V.)
- Subjects :
- Animals
Cell Line
Cells, Cultured
Glaucoma metabolism
Glaucoma pathology
Humans
Jurkat Cells
Male
Neural Stem Cells metabolism
Rats, Sprague-Dawley
Ribonuclease, Pancreatic analysis
Trabecular Meshwork cytology
Trabecular Meshwork metabolism
Trabecular Meshwork pathology
Apoptosis
Glaucoma physiopathology
Intraocular Pressure
Neural Stem Cells pathology
Ribonuclease, Pancreatic metabolism
Trabecular Meshwork physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1862
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 26581172
- Full Text :
- https://doi.org/10.1016/j.bbadis.2015.11.005