Suppression of VEGF and Decrease in Vascular Leakage by Pyridoxal 5'-Phosphate in Diabetic Rats

PURPOSE: The authors of the present study investigated whether pyridoxal 5'-phosphate (PLP), an active coenzyme of vitamin B6, could inhibit the development of diabetic retinopathy in streptozotocin (STZ)-induced diabetic rats. METHODS: Seven-week-old Spraque-Dawley rats (n = 20) were used in the present study. STZ (70 mg/kg) was injected intraperitoneally to induce diabetes. Blood glucose and body weight were monitored. Intraperitoneal injections of 5 microg and 50 microg PLP were administered every two days from the second week of induced diabetes. During the third week of PLP injections, the concentration level of plasma homocysteine was measured. In addition, functional status was examined by vitreous fluorophotometer and anatomical status by vascular endothelial growth factor (VEGF) staining in the retina. RESULTS: Based on vitreous fluorophotometry examination, the PLP injection group proved to have a lower level of fluorescein concentration in the vitreous. Additionally, immunohistochemical staining revealed down-regulation of VEGF expression in the PLP group. In addition, the PLP group had a lower plasma homocysteine concentration. However, an over-dosage injection of PLP did not appear to have any noticeable impact on the treatment of diabetes. CONCLUSIONS: PLP, an active coenzyme of vitamin B6, proved to have inhibitory effects on VEGF expression and vascular leakage in the diabetic rat retina.

Measurement of Blood Retina Barrier in Branch Retinal Vein Occlusion (BRVO)

Vitreous fluorophotometry was used to measure blood retinal barrier permeability to fluorescein in 15 patients with branch retinal vein occlusion(BRVO). Mean posterior vitreous fluorescein concentration(3mm) was 20.0 +/- 11.3(ng/ml) in affected eyes, and 2.99 +/- 1.22(ng/ml) in unaffected eyes. There was a statistically significant difference between the affected eye and unaffected eye(p<0.05). Also there was a correlation between the hemorrhage area and the posterior vitreous fluorescein concentration(r2=0.819). This study revealed that the permeability of blood retinal barrier was increased in BRVO as compared to the contralateral eye, and the higher permeability values were associated with the extent of area involved.

The effect of subtenon injection of methylprednisolone acetate on the breakdown of blood retinal barrier after cryotherapy

Using computerized vitreous fluorophotometry (VFP, Fluorotron(TM)), we examined the effect of cryotherapy on the blood retinal barrier (BRB) and the effect of subtenon injection of methylprednisolone acetate (Depomedrol(R)). In experiment 1, the right eyes of the 13 pigmented rabbits were treated with heavy cryotherapy after baseline VFP readings. The freezes were applied at 6 places in each quadrant around the equator are in two rows, a total of 24 places circumferentially. The left eyes were reserved as controls. In 6 rabbits (cryo with steroid group), Depomedrol(R) 10 mg of Depomedrol was injected into subtenon space after cryotherapy. The other 7 rabbits were treated with cryotherapy only (cryo only group). The VFP readings were taken 1, 3, 5, and 7 days, 2, 3, 5, and 7 weeks after cryotherapy. Cryotherapy increased the breakdown of BRB significantly. The peak VFP readings were obtained 5 days after cryotherapy in the cryo only group and 7 days after cryotherapy in the cryo with steroid group. In the cryo only group, the severity of the breakdown of BRB was higher than in the cryo with steroid group, and the increased VFP readings could not be normalized until 7 weeks after cryotherapy. In experiment 2, both eyes of the 8 pigmented rabbits were treated with medium cryotherapy after baseline VFP readings. The freezes were applied at 3 places in the superior temporal quadrant and at 3 places in the superior nasal quadrant, a total of 6 places. Depomedrol(R) 10 mg was injected into subtenon space after cryotherapy in the right eyes only. The VFP readings were taken 1, 3, 5, 7, 10, and 14 days after cryotherapy. In this experiment, cryotherapy did not increase the breakdown of BRB. But in the right eye, the severity of the breakdown of BRB was significantly lower than in the left eye 7 and 10 days after cryotherapy. These results suggest that Depomedrol(R) can decrease the severity of the breakdown of BRB after cryotherapy, and may be useful in the prevention of proliferative vitreoretinopathy (PVR).