Purchase this article with an account.
Mariola Stanik, Khayyam Durrani, Timothy Hla; The Effect of Sphingosine 1-Phosphate Receptor Antagonism on VEGF-Induced Retinal Vascular Permeability. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4001.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Sphingosine 1-phosphate (S1P) has been shown to mediate vascular permeability in a variety of tissues. The purpose of this study is to investigate the effect of the recently synthesized S1P receptor antagonists JTE013, an S1P2 antagonist, and FTY720-P, a functional S1P1 antagonist, on VEGF-induced retinal vascular permeability, a mouse model of diabetic retinal edema.
Adult male BALB/ c mice were anesthetized and received combined intravitreal injections of 100 ng rhVEGF165 and 10 micromoles of JTE013, or FTY720-P in one eye and an equal dose of rhVEGF165 in the contralateral eye. Two hours later, 70 kd FITC-conjugated dextran was injected into the tail vein and allowed to circulate for 4 hours. Mice were then enucleated and retinas fixed with 4% PFA. Areas of leakage of FITC dextran were quantified and expressed as a percentage of total retinal area. In a separate experiment, 10 micromoles of VPC alone were injected in the vitreous cavity and compared to the contralateral eye injected with vehicle, following perfusion and fixation as previously described.
Intravitreal injection of JTE did not decrease VEGF-induced retinal vascular permeability compared to contralateral control eyes injected with VEGF alone (area of leakage: 3.52% +/- 1.48 vs. 3.39% +/- 1.87, p=0.96). Similarly, a significant change in vascular permeability was not observed with injection of intravitreal FTY-P (area of leakage: 6.68% +/- 2.28 vs. 5.07 +/- 1.54%, p=0.59). Finally in a separate experiment, injection of VPC alone did not alter retinal vascular permeability compared to vehicle injected control eyes (area of leakage: 2.49 +/- 0.69 vs. 3.16 +/- 1.61, p=0.69).
Intravitreal injection of JTE or FTY does not significantly alter VEGF-induced retinal vascular permeability in this model diabetic retinal edema. In addition, injection of VPC alone also does not alter retinal vascular permeability in normal mouse eyes at the dose studied. This is in contrast to observations of their effect of these modulators on skin and lung permeability, and confirms prior data on the variable effect of these molecules in selected organs.
This PDF is available to Subscribers Only