The role of Fas-FasL in the development and treatment of ischemic retinopathy.
OBJECTIVE
Define a role for Fas-FasL in oxygen-induced retinopathy and explore the mechanism of pigment-epithelium-derived growth factor (PEDF) inhibition in this model.


METHODS
Seven-day-old mice C57BL/6J (B6), FasL-defective (B6-gld), or Fas-defective (B6-lpr) mice were exposed to 75% oxygen for 5 days (postnatal day [P]7-P12) and returned to room air. On day P17, vascular architecture was assessed microscopically after perfusion with FITC-dextran, and preretinal nuclei were quantified by PAS and hematoxylin staining. In some experiments, mice were treated intraperitoneally with PEDF. Vascular architecture and preretinal nuclei counts were compared with those in PBS-treated control animals.


RESULTS
Oxygen-induced retinopathy was significantly increased in FasL-defective gld mice compared with wild-type B6 animals. This was manifested by an increase in the number of microaneurysms, neovascular tufts, and preretinal nuclei. PEDF treatment prevented retinopathy in B6, B6-gld, and B6-lpr mice.


CONCLUSIONS
Fas-FasL interactions regulate the extent of oxygen-induced retinal neovascularization. The inhibition of neovascularization in B6 gld, and B6-lpr mice by PEDF suggests that Fas-FasL interactions are probably not the mechanism for inhibition in this model.
Barreiro
Ramon
R
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Schadlu
Ramin
R
Herndon
John
J
Kaplan
Henry J
HJ
Ferguson
Thomas A
TA
D000818:Animals; D004195:Disease Models, Animal; D005136:Eye Proteins; D053222:Fas Ligand Protein; D005451:Fluorescein Angiography; D005838:Genotype; D018496:Hyperoxia / Q000150:complications; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D009414:Nerve Growth Factors; D011506:Proteins / Q000627:therapeutic use; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015843:Serpins / Q000627:therapeutic use; D019014:fas Receptor / Q000502:physiology*; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D011506:Proteins; D015843:Serpins; D019014:fas Receptor; D000099174:Pigment Epithelium-Derived Factor; C505658:Fasl protein, mouse