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Cited 2 time in webofscience Cited 2 time in scopus
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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

Authors
Kim, Kyoung WooPark, Soo HyunOh, Doo HwanLee, Seung HoonLim, Kyung SubJoo, KwangsicChun, Yeoun SookChang, Soo-IkMin, Kyong-MiKim, Jae Chan
Issue Date
Feb-2016
Publisher
ELSEVIER SCIENCE BV
Keywords
Angiogenin; Ribonuclease 5; Glaucoma; Intraocular pressure regulation; Trabecular meshwork cell; Anti-apoptosis
Citation
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v.1862, no.2, pp 145 - 154
Pages
10
Journal Title
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume
1862
Number
2
Start Page
145
End Page
154
URI
https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/7352
DOI
10.1016/j.bbadis.2015.11.005
ISSN
0925-4439
1879-260X
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. (C) 2015 Elsevier B.V. All rights reserved.
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