Oxygen-induced retinopathy in the mouse.
OBJECTIVE
To develop oxygen-induced retinopathy in the mouse with reproducible and quantifiable proliferative retinal neovascularization suitable for examining pathogenesis and therapeutic intervention for retinal neovascularization in retinopathy of prematurity (ROP) and other vasculopathologies.


METHODS
One-week-old C57BL/6J mice were exposed to 75% oxygen for 5 days and then to room air. A novel fluorescein-dextran perfusion method has been developed to assess the vascular pattern. The proliferative neovascular response was quantified by counting the nuclei of new vessels extending from the retina into the vitreous in 6 microns sagittal cross-sections. Cross-sections were also stained for glial fibrillary acidic protein (GFAP).


RESULTS
Fluorescein-dextran angiography delineated the entire vascular pattern, including neovascular tufts in flat-mounted retinas. Hyperoxia-induced neovascularization occurred at the junction between the vascularized and avascular retina in the mid-periphery. Retinal neovascularization occurred in all the pups between postnatal day 17 and postnatal day 21. There was a mean of 89 neovascular nuclei per cross-section of 9 eyes in hyperoxia compared to less than 1 nucleus per cross-section of 8 eyes in the normoxia control (P < 0.0001). Proliferative vessels were not associated with GFAP-positive astrocyte processes.


CONCLUSIONS
The authors have described a reproducible and quantifiable mouse model of oxygen-induced retinal neovascularization that should prove useful for the study of pathogenesis of retinal neovascularization as well as for the study of medical intervention for ROP and other retinal angiopathies.
Smith
L E
LE
Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
Wesolowski
E
E
McLellan
A
A
Kostyk
S K
SK
D'Amato
R
R
Sullivan
R
R
D'Amore
P A
PA
D000818:Animals; D003911:Dextrans; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D005452:Fluoresceins; D005654:Fundus Oculi; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D037102:Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015203:Reproducibility of Results; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000209:etiology / Q000378:metabolism / Q000473:pathology
D003911:Dextrans; D005452:Fluoresceins; D005904:Glial Fibrillary Acidic Protein; D037102:Lectins; C052526:fluorescein-dextran