title: The effect of retinal ganglion cell injury on light-induced photoreceptor degeneration.
abstract: OBJECTIVE
  To determine the effect of optic nerve transection (ONT) and excitotoxic retinal ganglion cell (RGC) injury on light-induced photoreceptor degeneration.
  
  
  METHODS
  Age- and sex-matched rats underwent unilateral ONT or received intravitreal injections of N-methyl-D-aspartate (NMDA). The fellow eye received sham treatment, and 7 or 21 days later each eye was subjected to an intense photic injury. Maximum a- and b-wave amplitudes of the flash electroretinogram (ERG) were measured at baseline, after the RGC insult, and 5 days after the photic injury. Semiquantitative reverse transcription-polymerase chain reaction analysis and immunoblot analysis were used to assess rod opsin mRNA and rhodopsin kinase protein levels and to measure defined trophic factors 7 or 21 days after ONT or injection of NMDA. Structural changes after the insults were determined histologically and immunohistochemically.
  
  
  RESULTS
  ONT caused time-dependent reductions in the mean a- and b-wave amplitudes. Seven days after intravitreal NMDA the b-wave amplitude was reduced, but the a-wave was unaffected. ONT and NMDA injection attenuated the light-induced reductions in the a- and b-wave. Rod opsin mRNA levels and rhodopsin kinase protein levels were also significantly greater in the axotomized and NMDA-treated eyes compared with the sham-treated fellow eyes after the photic injury. Structural protection in the RGC-injured eyes was also evident histologically. Fibroblast growth factor (FGF)-2, ciliary neurotrophic factor (CNTF), and glial fibrillary acidic protein (GFAP) were significantly upregulated after ONT and NMDA.
  
  
  CONCLUSIONS
  ONT and intravitreal injection of NMDA protect against subsequent photic injury. This protection may relate to the activation of retinal glial cells and the possible action of trophic factors such as FGF-2 and CNTF.
authors.affiliation: Nuffield Laboratory of Ophthalmology, Oxford University, Oxford, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Casson
authors.forename: Glyn
authors.initials: G
authors.lastname: Chidlow
authors.forename: John P M
authors.initials: JP
authors.lastname: Wood
authors.forename: Manuel
authors.initials: M
authors.lastname: Vidal-Sanz
authors.forename: Neville N
authors.initials: NN
authors.lastname: Osborne
mesh_terms: D000818:Animals; D019771:Axotomy; D020934:Ciliary Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D004596:Electroretinography; D005136:Eye Proteins; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D051606:G-Protein-Coupled Receptor Kinase 1; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D008027:Light; D016202:N-Methylaspartate / Q000633:toxicity; D009900:Optic Nerve / Q000601:surgery; D020419:Photoreceptor Cells, Vertebrate / Q000528:radiation effects*; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017299:Rod Opsins / Q000235:genetics; D015854:Up-Regulation
chemical_list: D020934:Ciliary Neurotrophic Factor; D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D017299:Rod Opsins; D016222:Fibroblast Growth Factor 2; D016202:N-Methylaspartate; D011494:Protein Kinases; D051606:G-Protein-Coupled Receptor Kinase 1; C496765:Grk1 protein, rat