Impairment of retinal vascular homeostasis is associated with the development and progression of diabetic retinopathy involving gap junction intercellular communication (GJIC) activity. The principal gap junction protein of intercellular communication, connexin, was investigated to determine the effects of high glucose concentrations on the expression of endothelial-specific connexins (Cx37, Cx40, and Cx43), connexin phosphorylation pattern, and GJIC activity. Rat microvascular endothelial (RME) cells grown in high (30 mmol/l)-glucose medium for 9 days had reduced Cx43 expression: Cx43 mRNA (68 ؎ 13% of control; P ‫؍‬ 0.019, n ‫؍‬ 5) and protein (55.6 ؎ 16% of control; P ‫؍‬ 0.003, n ‫؍‬ 5) levels were reduced; however, Cx37 and Cx40 expression was not affected. Using alkaline phosphatase and Western blot analyses, we identified three forms of Cx43: a nonphosphorylated form (P0) and two phosphorylated forms (P1 and P2). Expression of all three forms was decreased in cells grown in high-glucose medium: PO, 73 ؎ 15% of control (P ‫؍‬ 0.04); P1, 57 ؎ 16% of control (P ‫؍‬ 0.01); and P2, 42 ؎ 22% of control (P ‫؍‬ 0.006). Using immunofluorescence microscopy, we observed Cx43 localization at specific sites of contact (plaques) between adjacent cells. In cells grown in highglucose medium, we observed reduced plaque counts (63 ؎ 6% of control; P ‫؍‬ 0.009) and decreased intensity of Cx43 immunofluorescence compared with cells grown in normal medium. Furthermore, using scrape load dye transfer (SLDT) technique, we found that these cells exhibited reduced GJIC activity (60% of control; P ‫؍‬ 0.01, n ‫؍‬ 5). The reduction in GJIC activity correlated with the decreased Cx43 protein levels (r ‫؍‬ 0.9). These results indicate that high glucose concentrations inhibited GJIC activity by reducing Cx43 synthesis in RME cells. Impaired intercellular communication may contribute to breakdown of homeostatic balance in diabetic microangiopathy. Diabetes 51:1565-1571, 2002

High-glucose-induced downregulation of Cx43 expression and inhibition of GJIC in retinal pericytes may play a role in the disruption of vascular homeostasis in diabetic retinopathy.

The effect of combined antisense oligonucleotides (ASoligos) against overexpression of extracellular matrix (ECM) components, fibronectin, laminin, and collagen IV and on cell monolayer permeability was examined in rat microvascular endothelial cells (RMECs) grown in high glucose medium and on retinal vascular permeability in diabetic rats. RMECs grown in high glucose for 10 days and transfected with combined AS-oligos showed a significantly reduced fibronectin, laminin, and collagen IV protein level. In parallel studies, high-glucose-induced excess monolayer permeability was also reduced in RMECs transfected with the combined AS-oligos. Similarly, diabetic rats intravitreally injected with the combined AS-oligos and examined after 2 months of diabetes showed significant reduction in retinal fibronectin, laminin, and collagen IV expression. In addition, vascular permeability, as determined from extravasation of fluorescein isothiocyanate-BSA in the surrounding areas of the retinal capillaries, was partially reduced in the combined AS-oligos-treated diabetic retinas. Our results indicate that the combined AS-oligos strategy is effective in simultaneously reducing fibronectin, collagen IV, and laminin overexpression and reducing vascular leakage in the retinal capillaries of diabetic rat retinas. The findings suggest that abnormal synthesis of ECM components may contribute to vascular leakage in the diabetic retina. Diabetes 55: 86 -92, 2006

These results provide the first evidence that high glucose-induced downregulation of Cx43 expression is an early trigger for inducing apoptosis in microvascular endothelial cells. This finding may have important implications toward breakdown of vascular homeostasis and initiation of apoptosis in diabetic retinopathy.

In conclusion, the average time for the development of diabetic retinopathy from nonexistence to blindness was approximately 26.5 years. The present recommendation for annual screening in type 2 diabetics with nonproliferative diabetic retinopathy should be retained only for the mild form, not for the moderate or severe forms.

The purpose of this follow-up study was conducted to assess the incidence and risk factors of diabetic retinopathy (DR) among type 2 diabetics in Kinmen, Taiwan. A penal of eye screening regimes were performed yearly for 971 type 2 diabetics by two senior ophthalmologists using indirect ophthalmoscopy and 45-degree color fundus photography to examine fundus after dilating pupils from 1999 to 2002. 74.7% (725/971) of diabetics had been screened at least two times during this period. Among the 548 type 2 diabetics who had no DR at first screening, 93 subjects developed any type of DR. The 3-year 18.2% cumulative incidence was (95% CI: 14.8-21.5%) and incidence density was 6.62% per year (95% CI: 5.36-8.06% per year). Using Cox regression model, HbAlc revealed the significantly dose response relationship to the development of DR (chi2-test for trend = 9.41, p < 0.05) after controlling for confounding factors. Other independent predictors related to the development of DR included duration of diabetes (RR: 1.09, 95% CI: 1.05-1.13), higher systolic blood pressure (>140 vs. < 140 mm Hg, RR: 1.96, 95% CI: 1.23-3.12), and higher triglyceride (> 200 vs. < 200 mg/dl, RR: 1.60, 95% CI: 1.01-2.54). In conclusion, in addition to poor glycemic control of which is the most significant risk factor for the development of DR, longer duration of diabetes, higher systolic blood pressure, and elevated serum triglyceride levels were also associated with the development of DR among type 2 diabetics in Kinmen.

Thinner SFCT and longer axial length are significant risk factors for myopic maculopathy. Unlike previous epidemiological surveys, results of this clinic-based study suggested that systolic blood pressure is not a significant factor for maculopathy.

Purpose To evaluate the sensitivity and specificity of optical coherence tomography angiography (OCTA) in differentiating polypoidal choroidal vasculopathy (PCV) from age-related macular degeneration (AMD). Methods Fundus color photographs, spectral-domain optical coherence tomography, and fluorescein angiography (step 1) and OCTA (step 2) of 50 eyes that had PCV or AMD were presented to two ophthalmologists. The final diagnoses of PCV were masked. Sensitivity and specificity were calculated and compared to the 2-step approach (before and after OCTA) in detecting PCV. The limitations were also evaluated. Results Of the 50 eyes, 31 were PCV and 19 were non-PCV. The sensitivity increased from 69.5% to 90% after OCTA; however, there was no significant improvement in specificity after OCTA. 70.9% of the eyes with PCV had clear or obvious branching vascular nets (BVNs) in OCTA with high sensitivity (97.5%) after OCTA. Contrarily, 29.1% had insignificant BVNs with a low sensitivity (72.5%) after OCTA. 27% of the occult choroidal neovascularization (CNV) cases were overdiagnosed as PCV when OCTA was applied. Conclusions OCTA based on clear BVNs at the choroidal level increased sensitivity of diagnosis of PCV by 20%. However, the false-positive rate also increased in occult CNV. Several limitations for a correct diagnosis of PCV were noted.