title: Ribonuclease 5 coordinates signals for the regulation of intraocular pressure and inhibits neural apoptosis as a novel multi-functional anti-glaucomatous strategy.
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.
authors.affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea; Graduate School of Chung-Ang University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyoung Woo
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea.
authors.forename: Doo Hwan
authors.initials: DH
authors.lastname: Oh
authors.affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea.
authors.forename: Kyung Sub
authors.initials: KS
authors.lastname: Lim
authors.affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Kwangsic
authors.initials: K
authors.lastname: Joo
authors.affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea.
authors.forename: Yeoun Sook
authors.initials: YS
authors.lastname: Chun
authors.affiliation: Department of Biochemistry, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Soo-Ik
authors.initials: SI
authors.lastname: Chang
authors.affiliation: Department of Biochemistry, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Kyong-Mi
authors.initials: KM
authors.lastname: Min
authors.affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea. Electronic address: jck50ey@daum.net.
authors.forename: Jae Chan
authors.initials: JC
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002478:Cells, Cultured; D005901:Glaucoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007429:Intraocular Pressure; D019169:Jurkat Cells; D008297:Male; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D012259:Ribonuclease, Pancreatic / Q000032:analysis / Q000378:metabolism*; D014129:Trabecular Meshwork / Q000166:cytology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: C046366:angiogenin; D012259:Ribonuclease, Pancreatic
keywords: Angiogenin; Anti-apoptosis; Glaucoma; Intraocular pressure regulation; Ribonuclease 5; Trabecular meshwork cell