Figure 1.

Cyclic AMP analog, 8-CPT-AM, regulates retinal vascular permeability. A, Rap1 is found in the capillary plexus of the retina. Immunofluorescence analysis was utilized to detect the presence of Rap1 (green) in rat retina. IB4 vascular marker (purple) and Hoechst nuclear stain was used. Ganglion cell layer (GCL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL) are shown. Scale bars, 75 and 25 μm for zoom images. B, 8-CPT-AM blocks retinal vascular permeability. Long-Evans rats received intravitreal co-injection of VEGF (50 ng) and TNF-α (10 ng) or 8-CPT-AM at 355 ng (an estimated vitreous concentration of 10 μm) or 1.78 μg (estimated 50 μm) with VEGF and TNF-α and compared with vehicle control. After 3 h, rats received a femoral vein injection of Evan's Blue and retinal dye accumulation was determined. C, 8-CPT-AM reverses ischemia reperfusion-induced permeability. Retinal ischemia in mice was achieved by increasing the intraocular pressure with PBS delivered to the anterior chamber to prevent blood flow for 90 min followed by natural reperfusion. 48 h later vehicle or 8-CPT-AM at 278 ng (estimated vitreous concentration of 100 μm) was delivered by intravitreal injection and FITC-BSA dye accumulation was determined. Results are expressed as the mean relative to the control ± S.D., Bonferroni post hoc test, ##, p < 0.01 compared with control.