Retinal expression, regulation, and functional bioactivity of prostacyclin-stimulating factor.

Prostacyclin-stimulating factor (PSF) acts on vascular endothelial cells to stimulate the synthesis of the vasodilatory molecule prostacyclin (PGI2). We have examined the expression, regulation, and hemodynamic bioactivity of PSF both in whole retina and in cultured cells derived from this tissue. PSF was expressed in all retinal cell types examined in vitro, but immunohistochemical analysis revealed PSF mainly associated with retinal vessels. PSF expression was constitutive in retinal pericytes (RPCs) but could be modulated in bovine retinal capillary endothelial cells (RECs) by cell confluency, hypoxia, serum starvation, high glucose concentrations, or inversely by soluble factors present in early vs. late retinopathy, such as TGF-beta, VEGF, or bFGF. In addition, RPC-conditioned media dramatically increased REC PGI2 production, a response inhibited by blocking PSF with a specific antisense oligodeoxynucleotide (ODN). In vivo, PGI2 increased retinal blood flow (RBF) in control and diabetic animals. Furthermore, the early drop in RBF during the initial weeks after inducing diabetes in rats, as well as the later increase in RBF, both correlated with levels of retinal PSF. RBF also responded to treatment with RPC-conditioned media, and this effect could be partially blocked using the antisense PSF ODN. We conclude that PSF expressed by ocular cells can induce PGI2, retinal vascular dilation, and increased retinal blood flow, and that alterations in retinal PSF expression may explain the biphasic changes in RBF observed in diabetes.

Changes in blood-retinal barrier permeability in form deprivation myopia in tree shrews.

To study the correlation between blood-retinal barrier (BRB) permeability and development of form deprivation (FD) myopia, FD was induced in tree shrews. The refractive error and the axial dimensions of the optical elements were measured. Ocular fluorescence was measured before and after fluorescein-Na injection. The inward permeability (P(in)) of the BRB was measured before and 15, 30, and 45 days after FD was induced. FD eyes became significantly myopic 15 days after FD was induced (P<0.01), and myopia progressed 45 days after FD was induced compared with untreated controls. Neither anterior chamber length nor lens thickness changed significantly. The vitreous chamber in FD eyes, however, was significantly elongated from 15 days after FD was induced (P<0.01) compared with controls. The P(in) ratio (P(in) [FD eye]/P(in) [untreated control]), increased significantly 45 days after FD was induced (P<0.05). In FD myopia in tree shrews, the BRB permeability increases abnormally. Impaired BRB function might be a secondary effect of myopia development rather than the cause of myopia.

Comparison of short- and long-term effects of betaxolol and timolol on human retinal circulation.

PURPOSE: To determine the short- and long-term effects of betaxolol and timolol on human retinal circulation. METHODS: In a double-masked, randomised, placebo-controlled study we evaluated the effects of both a one-drop application and a twice-daily 2-week application of either topical 0.5% betaxolol hydrochloride or topical 0.5% timolol maleate on the retinal circulation in 12 healthy volunteers. Laser Doppler velocimetry was used to detect changes in the retinal venous blood flow. RESULTS: In both betaxolol- and timolol-treated eyes, intraocular pressure decreased significantly compared with baseline values after both 90 min and 2 weeks. In betaxolol-treated eyes, retinal blood flow did not change significantly after 90 min, but increased significantly (14 +/- 9%; p = 0.02) compared with baseline after 2 weeks. In timolol-treated eyes, retinal blood flow decreased significantly (18 +/- 5%: p = 0.04) compared with baseline after 90 min, and also decreased significantly (14 +/- 6%; p = 0.04) compared with baseline after 2 weeks. CONCLUSIONS: Retinal blood flow increases as a long-term effect of betaxolol and decreases as both a short- and long-term effects of timolol.

Diurnal variation of corneal autofluorescence in normal and diabetic eyes.

PURPOSE: To examine the diurnal variations in corneal autofluorescence in normal and diabetic patients. METHODS: We measured corneal autofluorescence using a fluorophotometer fitted with an anterior segment adapter. Corneal autofluorescence was measured 10 times at 3 min intervals to evaluate the reproducibility of this instrument in 4 eyes of 4 normal subjects. The diurnal variation in corneal autofluorescence was determined by measuring the fluctuations in 10 eyes in 10 normal subjects and one unoperated eye each of 10 patients with proliferative diabetic retinopathy (PDR). We performed five consecutive measurements at 1000, 1130, 1400, 1630 and 1900 hours. The mean value of five measurements, the variation range and the coefficient of variation were analysed. RESULTS: The mean coefficient of variation in the measurement using this instrument was 8.6 +/- 1.0%. In the patients with PDR, the mean corneal autofluorescence value was significantly higher (p < 0.001), the variation range was significantly wider (p < 0.001) and the coefficient of variation was significantly greater (p < 0.01) than in the normal subjects. CONCLUSIONS: The results of this study suggest that corneal autofluorescence changes over the course of a day in patients with diabetes. This may be caused by the breakdown of the blood-aqueous barrier that we reported previously.