title: Effects of single intravitreal rhEPO injection on light-induced retinal injury in rats.
abstract: OBJECTIVE
  To observe the effects of a single intravitreal rhEPO injection on light-induced retinal damage in rats and to explore the possible mechanisms.
  
  
  METHODS
  Male Sprague-Dawley rats were randomly divided into a normal group, a control group (PBS intravitreal injection), and a number of treatment groups (intravitreal rhEPO injection at 0.625, 1.25, 2.5, 5, 10, or 20 U). After dark adaptation for 24 h, rats were exposed to white light (2800 lx) for 5 h. Based on the effects of rhEPO on the ERG-b wave, an optimal dose (5U) was chosen for further experiments that included histopathological examination and outer nuclear layer (ONL) counting at 5 and 10 days after light exposure. Cell apoptosis and proteins (caspase-3, bcl-xL) were also examined at 3 days. Some cell signaling related proteins (AKT, ERK1/2 and STAT5) were also analyzed. In another experiment, rats received intravitreal injection of rhEPO (5U) at 30 min after light exposure. ERG and morphological changes were examined at 3 days after light exposure.
  
  
  RESULTS
  ERG-b wave amplitudes are well preserved in rats receiving 2.5, 5, or 10 U rhEPO, in comparison with the PBS control. The dose-effect relationship was bell-shaped, with the maximum effect at 5 U. Less apoptotic cells were in the ONL in the 5U group. The rats receiving 5 U rhEPO at 30 min after light exposure also had higher b-wave amplitude. Caspase-3 expression was down-regulated and Bcl-xL was up-regulated in the rhEPO group. Phosphorylated ERK(1,2) was reduced in the rhEPO group.
  
  
  CONCLUSIONS
  A single intravitreal injection of rhEPO can postpone photoreceptor light damage in rats. The optimal dose was 5 U in this study. The effective time window was from 24 h prior to light exposure to 5 h after. RhEPO may be involved in the regulation of the expression of Caspase-3 and Bcl-xL. The possible cell signal transduction maybe through the ERK1/2 pathway.
authors.affiliation: Ophthalmology Department, First People's Hospital, an Affiliate of Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Gong
authors.forename: Yating
authors.initials: Y
authors.lastname: Qiu
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Song
authors.forename: Qin
authors.initials: Q
authors.lastname: Gu
authors.forename: Xingwei
authors.initials: X
authors.lastname: Wu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D058449:Intravitreal Injections; D008027:Light / Q000009:adverse effects*; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D008297:Male; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012160:Retina / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D050799:STAT5 Transcription Factor / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494813:Bcl2l1 protein, rat; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; D051020:bcl-X Protein; D004921:Erythropoietin; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D053148:Caspase 3