title: Increased retinal neovascularization in Fas ligand-deficient mice.
abstract: OBJECTIVE
  To investigate whether the absence of the Fas-Fas ligand system of apoptosis regulation affects hyperoxia-induced retinal vaso-obliteration and retinal neovascularization in a mouse model of oxygen-induced retinopathy.
  
  
  METHODS
  C57BL/6 (B6) and congenic Fas ligand-deficient generalized lymphoproliferative disease (gld) mice were exposed to 75% oxygen from postnatal day (P)7 to P12 and then allowed to recover in room air. Eyes obtained from P7, P8, P10, P12, P14, P17, and P21, from both hyperoxia-injured and room air control animals were processed for histopathologic examination. Retinopathy was also qualitatively assessed in FITC-dextran perfused retinas by fluorescence microscopy. TUNEL assays were used to compare apoptosis in B6 and gld mice. Intraretinal blood vessel formation was quantitated by immunolabeling with an anti-type-IV collagen antibody. Retinopathy was further assessed by quantitation of preretinal neovascular nuclei on P17. RT-PCR was used to examine retinal expression of Fas and Fas ligand (FasL) over a time course of hyperoxia-induced retinopathy.
  
  
  RESULTS
  In hyperoxia-injured mice, the same degree of vaso-obliteration was apparent on P8, P10, and P12 in B6 and gld mice. By P17, the hyperoxia-exposed FITC-perfused retinas of both strains exhibited preretinal neovascular tufts. However, P17 gld hyperoxia-exposed retinas exhibited approximately a 50% increase in preretinal neovascular nuclei compared with B6 mice. In addition, a subset of apoptotic cells located solely within the neovascular tufts on P17 were significantly decreased in hyperoxia-exposed gld retinas, compared with B6 control animals. RT-PCR showed an increase in the expression levels of Fas in both strains of mice as a result of hyperoxia-induced injury.
  
  
  CONCLUSIONS
  These data suggest that the Fas-FasL interaction plays an important role in retinal neovascularization after hyperoxia-induced injury. The absence of functional FasL leads to an increased incidence of preretinal neovascular nuclei and decreased retinal apoptosis suggesting that this pathway may serve as a means of regulating endogenous endothelial cell populations in pathologic angiogenesis.
authors.affiliation: Department of Pediatrics, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Davies
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Eubanks
authors.forename: Michael R
authors.initials: MR
authors.lastname: Powers
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D005451:Fluorescein Angiography; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism* / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007231:Infant, Newborn; D008024:Ligands; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008856:Microscopy, Fluorescence; D015861:Retinal Neovascularization / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism* / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019014:fas Receptor / Q000502:physiology*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor