Abstract
Purpose :
Developing novel anti-angiogenic therapies distinct from VEGF is critical for the identification of new treatments for neovascular age-related macular degeneration. Oncostatin M (OSM), a member of the IL-6 cytokine family, has been identified as an endothelial cell (EC) mitogen in vitro and in vivo. We investigated the effect of OSM in a laser-induced choroidal neovascularization (CNV) model.
Methods :
C57BL/6J mice (6–8 weeks) were anesthetized before CNV lesions were induced by laser photocoagulation. Four laser burns were typically induced around the optic disc in each eye. Different doses of OSM (10 ng and 50 ng), aflibercept and PBS were injected intravitreally in a 1 μl volume. Optical coherence tomography angiography (OCT-A) imaging of the retina in adult mice was performed 7 days after OSM injection. Choroid–sclera complexes and retinas were separated and immunofluorescence (IF) was performed to evidence the vasculature and the inflammatory cells by whole-mount staining of both retina and choroidal tissues. The macrophage characterization was assessed by flow cytometry. Retina and choroid mRNA expression was tested by RT-qPCR.
Results :
In the CNV model, intravitreal injection of OSM 10 ng was found to inhibit neovascularization to the same extent as aflibercept. However, the group exposed to 50 mg of OSM showed no differences compared to the control. In the OSM 10 ng group, a higher infiltration of macrophages was found compared to PBS. Furthermore, the IL-6 gene expression was higher compared to PBS in the retina/choroid complex. Interestingly, OSM 10 ng induced a shift towards an M2 (CD206+) subtype of macrophage than M1 (CD80+).
Conclusions :
The intravitreal injection of OSM decreased vascular density and inhibited laser-induced CNV. Surprisingly, only the lower concentration of OSM led to a choroidal neovascularization inhibition and macrophage infiltration, whether 50 ng of OSM showed no reduction in vascular density compared to the PBS, due to feedback inhibition. We found that the two concentrations induced different gene transcription, especially of IL-6; in particular, OSM 10 ng showed a stimulating effect on the IL-6 mRNA expression. This might be related to asymmetry in macrophage infiltration (M2), and we speculate whether they could be the effectors of the anti-angiogenic effect shown by OSM on choroidal neovascularization.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.