An-Fei Li

Prevalence and Associated Risk Factors of Age-Related Macular Degeneration in an Elderly Chinese Population in Taiwan : The Shihpai Eye Study

PURPOSE To assess the prevalence and associated risk factors of age-related macular degeneration (AMD) in an elderly Chinese population in Taiwan. METHODS The Shihpai Eye Study was a survey of vision and ocular disease in an elderly Chinese population 65 years of age or older residing in Shihpai, Taipei, Taiwan. Of 2045 elderly residents randomly sampled from the household registration databank, 1361 (66.6%) underwent a detailed ophthalmic examination that included fundus color slides by fundus camera after pupil dilatation. Photographs were graded according to the Wisconsin Age-Related Maculopathy Grading System. RESULTS Fundus photographs were available for 1105 (54.0% in the eligible, 81.2% in the ocular examined) participants. The 47 (4.3%) participants who had ungradable fundus images were older and had more lens opacity. Of the 1058 gradable photographs, the prevalence of early AMD was 9.2% (95% confidence interval [CI], 7.8-10.8); of late AMD, 1.9% (95% CI, 1.3-2.7); of soft drusen, 42.2% (95% CI, 39.7-44.8); of soft indistinct drusen, 4.1% (95% CI, 3.1-5.2); and of any pigmentary change, 8.6% (95% CI, 7.2-10.2). Age was the most significant factor associated with both early and late AMD. The prevalence of early AMD rose from 5.0% in the 65- to 69-year age group to 24.4% in those 80 years of age and older; and for late AMD, from 1.0% to 9.0%. Those who currently drank alcohol had a lower rate of early AMD than did the nondrinker (adjusted odd ratio 0.32, 95% CI: 0.11-0.93, P = 0.037). CONCLUSIONS AMD is a common eye disease in the elderly Chinese people in Taiwan. The adjusted prevalence rate of exudative AMD is comparable to that in the Chinese people in the Multiethnic Study of Atherosclerosis (MESA) in the United States but is higher than in the Chinese people in the Beijing study in China. Further studies are needed to clarify the incidence and associated risk factors.

High glucose-induced downregulation of connexin 43 expression promotes apoptosis in microvascular endothelial cells.

PURPOSE This study aims to determine whether high glucose-induced inhibition of connexin 43 (Cx43) expression and reduced gap junction intercellular communication (GJIC) promote microvascular endothelial cell loss. METHODS To downregulate Cx43 protein expression in rat microvascular endothelial cells (RMECs), the cells were grown in high (30 mM) glucose medium for 7 days, or transfected with antisense-Cx43 (AS-Cx43) oligonucleotides. Western blot analysis confirmed significant inhibition of Cx43 protein expression. Scrape load dye transfer (SLDT) assay showed significant reduction in GJIC activity in these cells compared to cells grown in normal medium or transfected with random oligonucleotides. In parallel, Cx43 immunostaining showed significant decrease in number of Cx43 plaques in cells with reduced Cx43 expression. DNA ladder assay, TUNEL assay, and differential staining were performed to identify cells undergoing apoptosis. RESULTS DNA ladder analysis, TUNEL assay, and differential staining indicated a significant increase in the number of apoptotic cells when Cx43 protein expression was reduced in both high-glucose cells or cells transfected with AS-Cx43 oligonucleotides with concomitant downregulation of GJIC activity. Additionally, DNA fragmentation, which was evident in cells with reduced Cx43 expression, suggested early phases of apoptosis. CONCLUSIONS 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.

Assessing the Natural Course of Diabetic Retinopathy: A Population-Based Study in Kinmen, Taiwan

Purpose: To explore the natural course of diabetic retinopathy among type 2 diabetics using the indirect ophthalmoscope and single-field fundus photographs in Kinmen, Taiwan. Methods: A screening program for diabetic retinopathy was carried out by a panel of ophthalmologists, who employed the ophthalmoscope and 45-degree retinal color photographs to examine the fundus after pupil dilation. Screening, which was conducted between 1999 and 2002, involved 971 patients diagnosed with type 2 diabetes. A multi-state Markov model was used to assess the natural course of diabetic retinopathy among type 2 diabetics. Results: Among the 725 diabetes patients who attended at least two ophthalmological fundus check-ups and were screened, the overall response rate was about 75%. The mean duration of the disease states mild nonproliferative diabetic retinopathy, moderate nonproliferative diabetic retinopathy, severe nonproliferative diabetic retinopathy, and proliferative diabetic retinopathy were 4.05 [95% confidence interval (CI): 3.28–5.32], 4.18 (95% CI: 3.18–6.06), 2.52 (95% CI: 1.78–4.27), and 4.22 (95% CI: 2.88–7.81) years, respectively. Compared to controls, the incidence of blindness reduction for annual, biennial, 3-year, 4-year, and 5-year screenings of diabetic retinopathy were approximately 94.4% (95% CI: 91.6%–96.3%), 83.9% (95% CI: 83.6%–84.2%), 70.2% (95% CI: 69.8%–70.7%), 57.2% (95% CI: 56.7%–57.7%), and 45.6% (95% CI: 45.0%–46.1%), respectively. Conclusions: 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.

Population-based study of nonproliferative diabetic retinopathy among type 2 diabetic patients in Kinmen, Taiwan

PurposeThis study was conducted to assess the prevalence and associated factors of nonproliferative diabetic retinopathy among type 2 diabetic patients in Kinmen, Taiwan.MethodsFrom 1991 to 1993, 971 type 2 diabetic patients in Kinmen underwent diabetic retinopathy screening performed by a panel of ophthalmologists using indirect ophthalmoscopy and 45° color fundus retinal photographs.ResultsOf the 971 patients screened in 1991–1993, 578 (59.5%) were examined for this study. Diabetic retinopathy was diagnosed in 127 patients (22.0%), including nonproliferative diabetic retinopathy in 13.3%, proliferative diabetic retinopathy in 1.4%, legal blindness in 1.4%, and ungradable diabetic retinopathy in 5.9%. Significant associated factors of nonproliferative diabetic retinopathy based on multiple logistic regression analysis were fasting plasma glucose (FPG) at baseline [≥126 mg/dl vs. <126 mg/dl; odds ratio (OR) = 2.89; 95% confidence interval (CI), 1.01–9.09], 2-h postload at baseline (≥200 vs. <200 mg/dl; OR = 1.48; 95% CI, 1.09–2.07); HbA1c at follow-up (≥7% vs. <7%; OR = 6.54; 95% CI, 3.01–14.20), duration of diabetes (≥15 years vs. <10 years; OR = 6.72; 95% CI, 2.13–21.18), and incremental systolic blood pressure between baseline and follow-up (OR = 1.02; 95% CI, 1.00–1.04).ConclusionsIn addition to the longer duration of type 2 diabetes, FPG at baseline, poorly controlled glucose concentration, and altered blood pressure may increase the risk of nonproliferative diabetic retinopathy in type 2 diabetic patients. Jpn J Ophthalmol 2006;50:44–52

Antisense oligonucleotides modulate high glucose-induced laminin overexpression and cell proliferation: a potential for therapeutic application in diabetic microangiopathy.

Vascular basement membrane (BM) thickening is a prominent and characteristic lesion of diabetic microangiopathy. Studies suggest that increased synthesis of laminin, a BM component, is associated with the development of thickened BM in diabetic vessels. In this study, we evaluated whether an interventive strategy using laminin antisense phosphorothioate oligonucleotides (Lam AS-oligos) could specifically inhibit high-glucose-induced laminin gene overexpression in vascular endothelial cells and normalize cell proliferation. Rat endothelial cells grown in high-glucose (30 mM) medium for 7 days showed increased laminin mRNA and protein level (195% +/- 28% of control, p < 0.05; 143% +/- 26% of control, p < 0.05, respectively) and reduced cell number (79% +/- 6% of control, p < 0.05) compared with cells grown in normal (5 mM) glucose medium. When cells grown in high-glucose medium were transfected with 0.4 microM Lam AS-oligos for 48 hours in the presence of 8 microM lipofectin, the laminin mRNA and protein level decreased (121% +/- 19% and 99% +/- 15% of control, respectively), and the cell number was restored to near normal level (93% +/- 7% of control). The results indicate that the antisense strategy is effective in selectively reducing laminin overexpression and improving endothelial cell proliferation under high-glucose conditions. Thus, the As-oligos may be potentially useful for preventing the development of thickened vascular BM in diabetic microangiopathy.