title: Protection of pattern electroretinogram and retinal ganglion cells by oncostatin M after optic nerve injury.
abstract: Injury to retinal ganglion cell (RGC) axons leads to selective loss of RGCs and vision. Previous studies have shown that exogenous neurotrophic factors promote RGC survival. We investigated the neuroprotective effects of oncostatin M (OSM), a member of the IL-6 family of cytokines, on pattern electroretinogram (PERG) and RGC survival after optic nerve crush (ON-crush) in the mouse. BALB/C mice received ON-crush in the left eyes for either 4-second or 1-second duration (4-s or 1-s). Fluoro-gold retrograde labeling was used to identify RGCs. RGC function was assessed by PERG measurement. OSM or CNTF protein was injected intravitreally immediately after ON-crush. OSM responsive cells were identified by localization of increased STAT3 phosphorylation. Significant higher RGC survival (46% of untreated control) was seen in OSM-treated eyes when assessed 2 weeks after 4-s ON-crush as compared to that (14% of untreated control) of the PBS-treated eyes (P<0.001). In addition, PERG amplitude was significantly higher in eyes treated with OSM or CNTF 1 week after 1-s ON-crush (36% of baseline) as compared with the amplitude of PBS-treated eyes (19% of the baseline, P = 0.003). An increase in STAT3 phosphorylation was localized in Müller layer after OSM treatment, suggesting that Müller cells mediate the effect of OSM. Our results demonstrate that one single injection of either OSM or CNTF after ON-crush improves RGC survival together with their electrophysiological activity. These data provide proof-of-concept for using neurotrophic factors OSM and CNTF for RGC degenerative diseases, including glaucoma and acute optic nerve trauma.
authors.affiliation: Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, Florida, United States of America; Department of Ophthalmology, Shanghai First People's Hospital, Jiaotong University, Shanghai, China; Shanghai Key Laboratory for Ocular Fundus Diseases, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xia
authors.affiliation: Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Rong
authors.initials: R
authors.lastname: Wen
authors.affiliation: Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Tsung-Han
authors.initials: TH
authors.lastname: Chou
authors.affiliation: Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Zhengying
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Porciatti
mesh_terms: D000818:Animals; D004596:Electroretinography; D051379:Mice; D008807:Mice, Inbred BALB C; D053683:Oncostatin M / Q000494:pharmacology*; D020221:Optic Nerve Injuries / Q000503:physiopathology*; D010766:Phosphorylation; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D053683:Oncostatin M