OBJECTIVETo evaluate the role of different oxygen concentration (FiO2) and different period of oxygen exposure on oxygen-induced retinopathy (OIR) in neonatal mice and to provide evidences for proper clinical oxygen therapy.

METHODSTwo hundred and four 7-day-old (P7) C57BL/6J mice were exposed to different FiO2 30%, 50% and 75% for 5, 7 and 9 days. The mice were divided into eight groups: groups 1 - 3 (n = 24 in each) were exposed to 30% oxygen for 5, 7 and 9 days, respectively; groups 4 - 6 (n = 24 in each) were exposed to 50% oxygen for 5, 7 and 9 days, respectively; group 7 (n = 30) was exposed to 75% hyperoxia for 5 days; group 8 (n = 30) was exposed to room air. Proliferative neovascular responses were estimated by observing vascular patterns in adenosine diphosphate-ase (ADPase) stained retina flat-mounts and quantitated by counting the number of new vascular cell nuclei extending into the internal limiting membrane in cross-sections.

RESULTS(1) Vascular patterns in retina flat-mounts: a) When FiO2 was 30%, the entire vascular pattern was completely normal after 5 and 7 days exposure; although the deep vascular system seemed slightly constricted after 9 days exposure, it recovered 2 days later and matured at P21. b) When FiO2 was 50%, after 5 days exposure (group 4), the larger vessels constricted and central perfusion decreased moderately; after exposing to room air for 2 days, neovascularization was seen; however, the entire vascular pattern was almost normal at P17. After 7 days of exposure to 50% O2 (group 5), the vascular pattern recovered a bit, seemed to be better than that of group 4; after 9 days of exposure to 50% O2 (group 6), only slight constriction could be seen and it disappeared 2 days later and all vessels matured later. c) When FiO2 was 75%, after 5 days exposure to hyperoxia, the larger vessels became tortuous and constricted, central perfusion became decreased obviously; after exposing to room air for 2 days, neovascularization was seen; and this response was maximal at P17 - P21. However, the mortality of nurser mice and pups increased dramatically when the duration of hyperoxia was prolonged. (2) Quantitative results in cross-sections: neovascular nuclei extending into the vitreous reached (41.9 +/- 2.8) per section in 75% oxygen group, while less than 1 in every other groups, which was statistically different (P < 0.0001).

CONCLUSIONSFiO2 and the duration of hyperoxia could affect retinal vascular development. Low and moderate FiO2 could induce reversible vessel changes, while high FiO2 induced irreversible changes which should be avoided in clinic.