title: Stanniocalcin-1 protects retinal ganglion cells by inhibiting apoptosis and oxidative damage.
abstract: Optic neuropathy including glaucoma is one of the leading causes of irreversible vision loss, and there are currently no effective therapies. The hallmark of pathophysiology of optic neuropathy is oxidative stress and apoptotic death of retinal ganglion cells (RGCs), a population of neurons in the central nervous system with their soma in the inner retina and axons in the optic nerve. We here tested that an anti-apoptotic protein stanniocalcin-1 (STC-1) can prevent loss of RGCs in the rat retina with optic nerve transection (ONT) and in cultures of RGC-5 cells with CoCl2 injury. We found that intravitreal injection of STC-1 increased the number of RGCs in the retina at days 7 and 14 after ONT, and decreased apoptosis and oxidative damage. In cultures, treatment with STC-1 dose-dependently increased cell viability, and decreased apoptosis and levels of reactive oxygen species in RGC-5 cells that were exposed to CoCl2. The expression of HIF-1α that was up-regulated by injury was significantly suppressed in the retina and in RGC-5 cells by STC-1 treatment. The results suggested that intravitreal injection of STC-1 might be a useful therapy for optic nerve diseases in which RGCs undergo apoptosis through oxidative stress.
authors.affiliation: Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Korea.
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Ko
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Yun
authors.forename: Ju-A
authors.initials: JA
authors.lastname: Kim
authors.forename: Tae Eun
authors.initials: TE
authors.lastname: Kim
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Seok Hwan
authors.initials: SH
authors.lastname: Kim
authors.forename: Ki Ho
authors.initials: KH
authors.lastname: Park
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Oh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000633:toxicity; D019610:Cytoprotection / Q000187:drug effects*; D006023:Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D058449:Intravitreal Injections; D008297:Male; D020221:Optic Nerve Injuries / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: D006023:Glycoproteins; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D003035:Cobalt; C051795:teleocalcin; C018021:cobaltous chloride