Purpose:
IL-10 is essential for induction of immune privilege by antigens injected into the aqueous or vitreous. IL-10 is reported to inhibit angiogenesis induced by tumors and limb ischemia. We hypothesized that induction of IL-10 contributes to the antiangiogenic effects of intravitreally administered peptides and proteins.
Methods:
Neonatal mice raised in 75% oxygen from day 7 to day 12, were given an intravitreal injection of IL-10 (1 µl of 10µg /ml) on day 12, and maintained in room air for 5 more days. Fixed eyes were cryosectioned, and every 10th section was stained with fluorescein-conjugated Griffonia simplicifolia lectin, and sequential contiguous photographs were made of each section. Morphometric analysis of retinal vascular density and area of neovascularization (NV) was performed using Metamorph.
Results:
The area of NV in IL-10 treated eyes was 924 ± 859, 80% lower than the NV area (4504 ± 1692) in contralateral untreated eyes (P<0.00004; see graph). IL-10 acted selectively on NV: it had no effect on the either the area of intraretinal blood vessels, or the percent of inner nuclear area occupied by blood vessels (P>0.5 for each). To further consider whether IL-10 acted selectively, the fraction of the total vascular area that was NV (%NV) was analyzed in each eye. IL-10 substantially reduced the %NV from 8.3 % in untreated eyes to 2.8%; P<0.006).
Conclusions:
The potent inhibition produced by 10 ng of IL-10 -- and its half life of 2-4 hours in vivo -- indicate that the early period of retinal hypoxia may be a critical therapeutic window for prevention of neovascularization. These data raise the further possibility that endogenous production of IL-10 contributes to the antiangiogenic effect of intravitreally administered proteins. These results demonstrate that IL-10 is potent inhibitor of intravitreal, hypoxia-induced NV.
Keywords: neovascularization • inflammation • retinal neovascularization