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John T. Flynn, Quan Wen; C3a Receptor Antagonism SB 290157 Attenuates Murine Oxygen Injury Retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3981.
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© ARVO (1962-2015); The Authors (2016-present)
At the 2010 ARVO annual meeting we presented the first evidence that the complement system is involved in the pathogenesis of murine Oxygen Injury Retinopathy (OIR). We have now extended our study to explore the effect of a C3a Receptor Antagonist(C3a RA) SB 290157, a small non peptide molecule, on murine OIR.
Litters of new born mice were divided into 4 groups. On Day of Life (DOL) 5, SB 290157 1 mg per kilogram body weight is injected intraperitoneally into mice in Group 1 and Group 3; same volume solvent without SB 290157 is injected intraperitoneally into mice in Group 2 and Group 4. Mice in group 1 and 2 are raised in room air all the time. Mice in group 3 and 4 are raised in room air till DOL 7 when they are transferred into a 75+/-2% oxygen chamber for 5 days, on DOL 12 they are returned to room air. On DOL 17, the mice from all 4 groups are euthanized, the eyes are enucleated and retinas dissected. Retinas are then stained with Isolectin B4 and mounted on slides for vasculature pattern study.
Retinas from room air raised group 1 and 2 show normal developmental vasculature patterns. For retinas from oxygen exposed groups, in group 4 which is not SB 290157 injected, the retinas whole mounts show extensive capillary wipeout near the optic disc and extensive neovascularization tufts in periphery; in group 3 which is SB 290157 injected, there is significantly less capillary damage and less neovasculariztaion tufts all over the whole retinas. No ocular or systemic side effects of the SB290-157 were noted in the mice that received the drug.
C3a Receptor Antagonism SB 290157 does not interfere with normal retinal development and can attenuate the damage to the developing capillary bed in murine OIR.
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