title: EPO reduces reactive gliosis and stimulates neurotrophin expression in Muller cells.
abstract: To characterize Müller cell-mediated neuroprotective and neurotrophic functions of the erythropoietin (EPO)/EPO receptor (EpoR) system in diabetic rat retina. A single intravitreal injection of EPO (8 mU/eye) was administered in rats 4 or 24 weeks after diabetes onset. The results showed that intravitreal EPO ameliorated the up-regulation of GFAP and vimentin in the diabetic retina evaluated by immunofluorescence and Western blotting; but up-regulated BDNF and CNTF expressions, quantified by real-time PCR and ELISA, in the 24-week diabetic rat retinas. In vitro, BDNF and CNTF expressions were stimulated by EPO through both extracellular signal-regulated kinase1/2 (ERK1/2) and Akt pathways. The neuro-regenerative function of EPO, as indicated by promotion of neurite outgrowth, was corroborated in vitro. BDNF was involved in EPO-induced neurite outgrowth of primary rat retinal neurons. Exogenous EPO exerts neuroprotective and neurotrophic functions by attenuating reactive gliosis and promoting neurotrophic factors in Muller cells in diabetic retina. Signaling pathways that are responsible for these Muller cell-mediated EPO/EpoR functions may be therapeutic targets for diabetic retinopathy.
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Liu-Mei
authors.initials: LM
authors.lastname: Hu
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.forename: Jingfa
authors.initials: J
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Lei
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Shen
authors.forename: Yalan
authors.initials: Y
authors.lastname: Wu
authors.forename: Mei
authors.initials: M
authors.lastname: Qin
authors.forename: Yaprak Banu
authors.initials: YB
authors.lastname: Unver
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhong
authors.forename: Guo-Tong
authors.initials: GT
authors.lastname: Xu
authors.forename: Weiye
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000517:prevention & control*; D009414:Nerve Growth Factors / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D017931:DNA Primers; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D014746:Vimentin; D004921:Erythropoietin