title: Critical role of photoreceptor apoptosis in functional damage after retinal detachment.
abstract: OBJECTIVE
  Although apoptosis is assumed to play a pivotal role in retinal function loss, its mechanism and real influence on retinal function are still unclear. To investigate the relation between retinal function and apoptosis, we studied photoreceptor apoptosis in experimental retinal detachment (RD).
  
  
  METHODS
  We induced RD by subretinal injection of sodium hyaluronate in Brown Norway rats. Apoptotic photoreceptors were detected by TdT-dUTP Terminal Nick-End Labeling (TUNEL). To evaluate the function of the detached retina, electroretinograms (ERGs) were taken on day 1, 3 with corneal electrodes and full-field stimulation.
  
  
  RESULTS
  Apoptotic DNA fragmentation appeared 12 hours after RD, was most prominent on day 3, and decreased thereafter. The ERGs showed that the amplitudes of dark-adapted a-waves and light adapted 2 Hz b-waves decreased immediately after RD and continued to decrease over time. The administration of Fas/Fc chimera recombinant protein or a caspase inhibitor, Z-VAD.fmk, failed to prevent either photoreceptor apoptosis or retinal functional damage. In contrast, brain derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) significantly impeded both apoptosis and dysfunction. The ERGs recognized the functional changes sensitively, and these ERG changes correlated well to the amount of photoreceptor apoptosis. Immunohistochemical study showed that apoptosis-inducing factor (AIF), a novel caspase-independent apoptotic factor, was relocalized from mitochondria to the nucleus in this process.
  
  
  CONCLUSIONS
  The present results showed that apoptosis was a key phenomenon in the retinal dysfunction in RD and that this process was transmitted mainly by mitochondria-dependent pathways rather than Fas/Fas-L or downstream caspase dependent pathways.
authors.affiliation: Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Hisatomi
authors.forename: Taiji
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Goto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yamanaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Oshima
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Hata
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Hajime
authors.initials: H
authors.lastname: Inomata
authors.forename: Santos A
authors.initials: SA
authors.lastname: Susin
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D002452:Cell Count; D003574:Cytochrome c Group / Q000378:metabolism; D004596:Electroretinography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D005420:Flavoproteins / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D010786:Photoreceptor Cells / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011914:Rats, Inbred BN; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012163:Retinal Detachment / Q000473:pathology / Q000503:physiopathology*; D019014:fas Receptor / Q000378:metabolism
chemical_list: C494831:Aifm1 protein, rat; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D005420:Flavoproteins; D006133:Growth Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019014:fas Receptor; D020932:Nerve Growth Factor