Abstract
Purpose :
To clarify if intraperitoneal (i. p.) injection of an S1Pr3 inhibitor, CAY10444, performs therapeutic attenuation on laser-induced choroidal neovascularization (CNV) in mice. We reported that S1Pr3 expressed in vascular endothelial cells as well as macrophages and local mesenchymal cells are involved in neovascularization activity (Yasuda et al. Lab Invest 2021). We also reported that S1Pr3 gene knockout suppressed the development of laser-induced CNV, that was not further exaggerated by chemical S1Pr2 inhibition (Iwanishi et al. 2023 ARVO).
Methods :
C57BL/6-background WT mice of 6-8 week-old were used. Argon laser-photocoagulation (4 shots, 80 μm spot size, 0.1 sec. duration, 200 mW) was performed in both eyes of mice (n=10). CAY10444 (1.2 mg/kg, n = 5) or vehicle (0.1% DMSO in PBS 0.1ml, n = 5) were administered daily by i.p. injection until euthanasia at day 14. The size of CNV was measured at 2 weeks by software-assisted fluorescence angiography after sacrifice and enucleation.
Results :
Different from S1Pr3 gene deletion, i. p. injection of an S1Pr3 inhibitor, CAY10444, did not influence the size of mouse CNV as detected by fluorescence angiography.
Conclusions :
Systemic administration of a S1Pr3 antagonist does not reproduce the therapeutic inhibitory effects of S1Pr3 gene deletion on laser-induced CNV in mice.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.