Haidong Zou

Protective Effect of Perindopril on Diabetic Retinopathy Is Associated With Decreased Vascular Endothelial Growth Factor-to-Pigment Epithelium-Derived Factor Ratio : Involvement of a Mitochondria-Reactive Oxygen Species Pathway

OBJECTIVE This study aimed to verify whether the decreased vascular endothelial growth factor (VEGF)–to–pigment epithelium–derived factor (PEDF) ratio can serve as an indicator for the protective effect of angiotensin-converting enzyme inhibitors (ACEIs) on diabetic retinopathy (DR) and to investigate the role of mitochondrial reactive oxygen species (ROS) in the downregulated VEGF-to-PEDF ratio. RESEARCH DESIGN AND METHODS Diabetic rats and control animals were randomly assigned to receive perindopril or vehicle for 24 weeks, and bovine retinal capillary endothelial cells (BRECs) were incubated with normal or high glucose with or without perindopril. VEGF, PEDF, PPARγ, and uncoupling protein-2 (UCP-2) in the rat retinas or BREC extracts were examined by Western blotting and real-time RT-PCR. The levels of VEGF and PEDF in cell culture media were examined by ELISA. Mitochondrial membrane potential (Δψm) and ROS production were assayed using JC-1 or CM-H2DCFDA. RESULTS The VEGF-to-PEDF ratio was increased in the retina of diabetic rats; perindopril lowered the increased VEGF-to-PEDF ratio in diabetic rats and ameliorated the retinal damage. In BRECs, perindopril lowered the hyperglycemia-induced elevation of VEGF-to-PEDF ratio by reducing mitochondrial ROS. We found the decreased ROS production was a result of perindopril-induced upregulation of PPARγ and UCP-2 expression and the subsequent decrease of Δψm. CONCLUSIONS It is concluded that the protective effect of ACEI on DR is associated with a decreased VEGF-to-PEDF ratio, which involves the mitochondria-ROS pathway through PPARγ-mediated changes of UCP-2. This study paves a way for future application of ACEI in treatment of DR.

The Protective Effect of Perindopril on Diabetic Retinopathy is Associated with Decreased VEGF/PEDF Ratio: Involvement of a Mitochondria-ROS Pathway

OBJECTIVE This study aimed to verify whether the decreased vascular endothelial growth factor (VEGF)–to–pigment epithelium–derived factor (PEDF) ratio can serve as an indicator for the protective effect of angiotensin-converting enzyme inhibitors (ACEIs) on diabetic retinopathy (DR) and to investigate the role of mitochondrial reactive oxygen species (ROS) in the downregulated VEGF-to-PEDF ratio. RESEARCH DESIGN AND METHODS Diabetic rats and control animals were randomly assigned to receive perindopril or vehicle for 24 weeks, and bovine retinal capillary endothelial cells (BRECs) were incubated with normal or high glucose with or without perindopril. VEGF, PEDF, PPARγ, and uncoupling protein-2 (UCP-2) in the rat retinas or BREC extracts were examined by Western blotting and real-time RT-PCR. The levels of VEGF and PEDF in cell culture media were examined by ELISA. Mitochondrial membrane potential (Δψm) and ROS production were assayed using JC-1 or CM-H2DCFDA. RESULTS The VEGF-to-PEDF ratio was increased in the retina of diabetic rats; perindopril lowered the increased VEGF-to-PEDF ratio in diabetic rats and ameliorated the retinal damage. In BRECs, perindopril lowered the hyperglycemia-induced elevation of VEGF-to-PEDF ratio by reducing mitochondrial ROS. We found the decreased ROS production was a result of perindopril-induced upregulation of PPARγ and UCP-2 expression and the subsequent decrease of Δψm. CONCLUSIONS It is concluded that the protective effect of ACEI on DR is associated with a decreased VEGF-to-PEDF ratio, which involves the mitochondria-ROS pathway through PPARγ-mediated changes of UCP-2. This study paves a way for future application of ACEI in treatment of DR.

A genome-wide association study reveals association between common variants in an intergenic region of 4q25 and high-grade myopia in the Chinese Han population

High-grade myopia (HM) is highly heritable, and has a high prevalence in the Han Chinese population. We carried out a genome-wide association study involving 102 HM cases suffering from retinal degeneration, and 335 controls who were free from HM and fundus diseases. Significant single-nucleotide polymorphisms were replicated in two follow-up studies: stage I involved 2628 independent cases and 9485 controls, and stage II involved a further 263 cases and 586 HM-free controls. The results were combined in a meta-analysis. Cases and controls were drawn from the Chinese Han population. A locus in an intergenic region at 4q25, within MYP11 (4q22-q27, OMIM: 609994), was found to be associated with HM (rs10034228, P(meta) = 7.70 × 10(-13), allelic odds ratio = 0.81, 95% confidence interval 0.76-0.86). There are no known genes in the region but a number of expressed sequence tags (ESTs) have been located there, one of which (BI480957) has been reported to express in the native human retinal pigment epithelium. In addition, a predicted gene was identified in this region. The genes predicted protein sequence is highly similar to tubulin, beta 8 and beta-tubulin 4Q. Several previous studies have shown that tubulin plays an important role in eye development. Our result is compatible with a previous linkage study in the Han Chinese population (mapping in MYP11, 4q22-q27), and provides a more accurate locus for HM. Although there is insufficient evidence to indicate that expressed EST and the predicted gene play an important role in developing HM, this region merits further study as a candidate for the disease.

Comparison of Blue Light-Filtering IOLs and UV Light-Filtering IOLs for Cataract Surgery: A Meta-Analysis

Background A number of published randomized controlled trials have been conducted to evaluate visual performance of blue light-filtering intraocular lenses (IOL) and UV light-filtering intraocular lenses (IOL) after cataract phacoemulsification surgery. However, results have not always been consistent. Therefore, we carried out a meta-analysis to compare the effectiveness of blue light-filtering IOLs versus UV light-filtering IOLs in cataract surgery. Methods and Findings Comprehensive searches of PubMed, Embase, Cochrane Library and the Chinese BioMedical literature databases were performed using web-based search engines. Fifteen trials (1690 eyes) were included for systematic review, and 11 of 15 studies were included in this meta-analysis. The results showed that there were no significant differences in postoperative mean best corrected visual acuity, contrast sensitivity, overall color vision, or in the blue light spectrum under photopic light conditions between blue light-filtering IOLs and UV light-filtering IOLs [WMD = −0.01, 95%CI (−0.03, 0.01), P = 0.46; WMD = 0.07, 95%CI (−0.04, 0.19), P = 0.20; SMD = 0.14, 95%CI (−0.33, 0.60), P = 0.566; SMD = 0.20, 95%CI (−0.04, 0.43), P = 0.099]. However, color vision with blue light-filtering IOLs was significantly reduced in the blue light spectrum under mesopic light conditions [SMD = 0.74, 95%CI (0.29, 1.18), P = 0.001]. Conclusion This meta-analysis demonstrates that postoperative visual performance with blue light-filtering IOLs is approximately equal to that of UV light-filtering IOLs after cataract surgery, but color vision with blue light-filtering IOLs demonstrated some compromise in the blue light spectrum under mesopic light conditions.

Epidemiology survey of rhegmatogenous retinal detachment in Beixinjing District, Shanghai, China.

Purpose To investigate the recent incidence and related risk factors of rhegmatogenous retinal detachment (RRD) in Chinese people. Methods This study was an incidence survey based on data for 108,132 persons in Beixinjing District, Shanghai, China. Patients with RRD were inpatients, outpatients, and patients from the local health network. Patients with RRD were compared with control subjects who were matched by sex, age, and block of residence. Previous population data were used to estimate the whole and specific incidence of RRD. Some factors relevant to the incidence of RRD were found by comparing the patients with RRD with the control subjects. Results Between January 1996 and December 1999, 61 cases of RRD occurred. The annual incidence of RRD was 11.3 cases per 100,000 population in 1996, 14.1 cases per 100,000 population in 1997, 14.1 cases per 100,000 population in 1998, and 17.9 cases per 100,000 population in 1999. The average annual incidence was 14.4 cases per 100,000 population (95% confidence interval, 10.0–18.6). There were 29 males and 32 females with RRD. The incidence of RRD among persons older than 40 years was high, especially among those between 40 and 59 years of age. The proportion of individuals with high myopia (more than −6 diopters) was significantly higher in the patient group than in the control group (P < 0.001). Conclusion The annual incidence of RRD among a local Chinese population increased over 4 years. This disease is strongly associated with high myopia and age.

Bulbar conjunctival thickness measurements with optical coherence tomography in healthy chinese subjects.

PURPOSE To conduct in vivo measurements of the bulbar conjunctiva epithelial, stromal, and total thicknesses in healthy Chinese subjects using optical coherence tomography (OCT) and to compare the conjunctival thickness differences between sex and age. METHODS From January to July 2012, healthy Chinese subjects were recruited to undergo a Cirrus HD-OCT examination using the Anterior Segment 5 Line Raster scanning protocol. Ophthalmoscopy and slit-lamp examinations were performed on all eyes, along with the determination of visual acuity. The bulbar conjunctiva epithelial thickness, stromal thickness, and full thickness were measured on cross-sectional conjunctiva images. The average values of each parameter were compared between males and females and among eight age groups (<20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, and >80 years). RESULTS A total of 711 eyes in 711 subjects (average age 46.5 years) were included. The average conjunctiva epithelial, stromal, and full thickness measurements were 42.4 ± 7.4 μm, 197.7 ± 32.5 μm, and 240.1 ± 29.8 μm, respectively. No significant difference was found for any of the three parameters between sexes. The conjunctiva epithelial thickness values decreased significantly after age 20 and were then maintained at relatively low levels, followed by a sharp increase at 60 years of age. The conjunctiva stromal thickness decreased throughout the entire lifetime, and the full thickness decreased from the teenage to the elderly periods. CONCLUSIONS None of the Chinese conjunctiva epithelial, stromal, and full thickness was sex-related, but all of them were age-related.

The Status of Diabetic Retinopathy and Diabetic Macular Edema in Patients with Type 2 Diabetes: A Survey from Beixinjing District of Shanghai City in China

Diabetic macular edema (DME) is the major cause of vision loss in patients with diabetic retinopathy (DR). The purpose of this study was to assess the prevalence of DR and DME in a community in China and to analyze the characteristics of their optical coherence tomography (OCT) images. This study was an incidence survey based on data from 108,132 residents living in the Beixinjing District, Shanghai, China. Patients with DME came from the local health network. OCT was performed in 151 eyes of 100 type 2 diabetes patients with DR and 102 eyes of normal control subjects. Totally 795 cases were examined, and 215 of them were diagnosed to have DR. The average thickness of the macular fovea was 195.56 µm in 151 eyes from 100 random samples. Forty-six eyes had macular thickening. The statistical analysis showed that there was a positive correlation between the thickness of the macular fovea and –log of best-corrected visual acuity (r = 0.2869, p = 0.0004) as well as the severity of DR (p = 0.0003). However, there was no statistical significance between DME and posterior vitreous detachment. The images of OCT in DME included 3 types. Best-corrected visual acuity moderately correlated with retinal thickness. The macular thickness correlated with the severity of DR but not with posterior vitreous detachment.

Development and psychometric tests of the Chinese-version Low Vision Quality of Life Questionnaire.

Background/Aims:To develop and assess the psychometric validity of a Chinese language Vision Health related quality-of-life (VRQoL) measurement instrument for the Chinese visually impaired.Methods: The Low Vision Quality of Life Questionnaire (LVQOL) was translated and adapted into the Chinese-version Low Vision Quality of Life Questionnaire (CLVQOL). The CLVQOL was completed by 100 randomly selected people with low vision (primary group) and 100 people with normal vision (control group). Ninety-four participants from the primary group completed the CLVQOL a second time 2 weeks later (test–retest group). The internal consistency reliability, test–retest reliability, item-internal consistency, item-discrimination validity, construct validity and discriminatory power of the CLVQOL were calculated.Results: The review committee agreed that the CLVQOL replicated the meaning of the LVQOL and was sensitive to cultural differences. The Cronbach’s α coefficient and the split-half coefficient for the four scales and total CLVQOL scales were 0.75–0.97. The test–retest reliability as estimated by the intraclass correlations coefficient was 0.69–0.95. Item-internal consistency was >0.4 and item-discrimination validity was generally <0.40. The Varimax rotation factor analysis of the CLVQOL identified four principal factors. the quality-of-life rating of four subscales and the total score of the CLVQOL of the primary group were lower than those of the Control group, both in hospital-based subjects and community-based subjects.Conclusion: The CLVQOL Chinese is a culturally specific vision-related quality-of-life measure instrument. It satisfies conventional psychometric criteria, discriminates visually healthy populations from low vision patients and may be valuable in screening the local community as well as for use in clinical practice or research.

Time spent in outdoor activities in relation to myopia prevention and control: a meta-analysis and systematic review

Outdoor time is considered to reduce the risk of developing myopia. The purpose is to evaluate the evidence for association between time outdoors and (1) risk of onset of myopia (incident/prevalent myopia); (2) risk of a myopic shift in refractive error and c) risk of progression in myopes only. A systematic review followed by a meta‐analysis and a dose–response analysis of relevant evidence from literature was conducted. PubMed, EMBASE and the Cochrane Library were searched for relevant papers. Of the 51 articles with relevant data, 25 were included in the meta‐analysis and dose–response analysis. Twenty‐three of the 25 articles involved children. Risk ratio (RR) for binary variables and weighted mean difference (WMD) for continuous variables were conducted. Mantel–Haenszel random‐effects model was used to pool the data for meta‐analysis. Statistical heterogeneity was assessed using the I2 test with I2 ≥ 50% considered to indicate high heterogeneity. Additionally, subgroup analyses (based on participants age, prevalence of myopia and study type) and sensitivity analyses were conducted. A significant protective effect of outdoor time was found for incident myopia (clinical trials: risk ratio (RR) = 0.536, 95% confidence interval (CI) = 0.338 to 0.850; longitudinal cohort studies: RR = 0.574, 95% CI = 0.395 to 0.834) and prevalent myopia (cross‐sectional studies: OR = 0.964, 95% CI = 0.945 to 0.982). With dose–response analysis, an inverse nonlinear relationship was found with increased time outdoors reducing the risk of incident myopia. Also, pooled results from clinical trials indicated that when outdoor time was used as an intervention, there was a reduced myopic shift of −0.30 D (in both myopes and nonmyopes) compared with the control group (WMD = −0.30, 95% CI = −0.18 to −0.41) after 3 years of follow‐up. However, when only myopes were considered, dose–response analysis did not find a relationship between time outdoors and myopic progression (R2 = 0.00064). Increased time outdoors is effective in preventing the onset of myopia as well as in slowing the myopic shift in refractive error. But paradoxically, outdoor time was not effective in slowing progression in eyes that were already myopic. Further studies evaluating effect of outdoor in various doses and objective measurements of time outdoors may help improve our understanding of the role played by outdoors in onset and management of myopia.

Prevalence and risk factors of idiopathic epiretinal membranes in Beixinjing blocks, Shanghai, China.

Background To determine the prevalence and risk factors associated with idiopathic epiretinal membranes (iERM) in a Chinese population aged 60 years or older in Beixinjing Blocks, Shanghai. Methods This population-based study consisted of 3727 participants (89.7% of the eligible). It was performed to describe the prevalence of iERM and possible demographic, systemic, and ocular factors associated with iERM. Each participant underwent a standardized interview and comprehensive ophthalmic examination. iERM was identified and graded from retinal photographs. Then, a case-control study comparing the participants with vs. without iERM was performed to further study the associations between iERM and blood biochemical test results (including fasting plasma glucose, serum creatinine, total cholesterol, and triglyceride), ocular biological parameters (including the axial length, corneal curvature, refractive diopter, intraocular press, and anterior chamber depth), and the data of optical coherence tomography. Results The prevalence of iERM was 1.02%. iERM was significantly associated with diabetes (OR: 2.457; 95% CI: 1.137, 5.309) and a higher level of education (OR: 1.48; 95% CI: 1.123, 1.952). Blood biochemical test results and ocular biological parameters showed no significant differences between the iERM and control groups, whereas the incidence of posterior vitreous detachment in the iERM group was much higher than in the control group (26.5% vs. 8.8%), but this difference was not statistically significant. Moreover, the eyes with iERM had poorer visual acuity than the eyes without iERM (P<0.05). Conclusions In Beixinjing Blocks, Shanghai, iERM was relatively rare, was associated with diabetes and a higher level of education, and caused a substantial decrease in visual acuity.