Ningpu Liu

Noncoding variant in the complement factor H gene and risk of exudative age-related macular degeneration in a Chinese population.

PURPOSE To investigate whether the previously reported noncoding variant of the complement factor H (CFH) gene and two coding variants of the complement component 3 (C3) gene are associated with exudative age-related macular degeneration (AMD) in Chinese patients. METHODS One hundred fifty Chinese patients with exudative AMD and 161 control individuals without AMD were recruited for the study. Genomic DNA was extracted from blood leukocytes. The noncoding variant of the CFH gene (rs1410996) and two coding variants of the C3 gene (rs2230199 and rs1047286) were genotyped by polymerase chain reaction (PCR) followed by allele-specific restriction enzyme digestion and direct sequencing. RESULTS Significant association was detected for exudative AMD with the CFH noncoding variant rs1410996. Frequencies of the risk C allele at rs1410996 were 72.0% in AMD cases versus 55.6% in controls (P < 0.001). The odds ratio for risk of AMD was 1.71 (95% confidence interval [CI], 0.82-3.54) for heterozygous TC genotype and 3.85 (95% CI, 1.84-8.05) for homozygous CC genotype compared with the wild TT genotype. In contrast, the C3 variants rs2230199 and rs1047286 were not associated with exudative AMD in the studied subjects. Frequencies of the risk G allele at rs2230199 and of the risk T allele at rs1047286 were 0.3% to 1.0% in both cases and controls. CONCLUSIONS The data suggest that the noncoding variant rs1410996 of the CFH gene moderately increased the risk of exudative AMD in a Chinese population. The C3 variants were rare and not associated with exudative AMD in this Chinese cohort.

Serum Carotenoids And Risk Of Age-related Macular Degeneration In A Chinese Population Sample

PURPOSE It has been hypothesized that the macular carotenoids protect against age-related macular degeneration (AMD). In this study, the association between serum concentrations of carotenoids and the presence of AMD was evaluated in a case-control sample of elderly Chinese subjects. METHODS Two hundred sixty-three individuals aged between 50 and 88 years enrolled in the study. Subjects included 82 cases with exudative AMD, 92 cases with early AMD, and 89 control individuals. Serum carotenoids (lutein, zeaxanthin, lycopene, α- and β-carotenes, and β-cryptoxanthin) and retinol were measured with reversed-phase high-performance liquid chromatography (HPLC). RESULTS Serum levels of carotenoids and retinol were significantly lower in the cases with exudative AMD than in the controls. Median levels of lutein and zeaxanthin were 0.538 and 0.101 μM, respectively, in the control subjects, and 0.488 and 0.076 μM, respectively, in cases with exudative AMD. After adjustment for age, sex, smoking status, and body mass index (BMI), a significant inverse association was observed for exudative AMD with serum zeaxanthin (relative risk ratio [RRR], 0.04; 95% confidence interval [CI], 0-0.35), lycopene (RRR, 0.22; 95% CI, 0.1-0.48), and α-carotene (RRR, 0.24; 95% CI, 0.12-0.51). Early AMD was inversely associated only with lycopene (RRR, 0.49; 95% CI, 0.28-0.86) but was positively associated with α-carotene (RRR, 2.22; 95% CI, 1.37-3.58). No significant associations were observed between serum lutein and cases with early or exudative AMD. CONCLUSIONS The data suggest that higher levels of serum carotenoids, in particular zeaxanthin and lycopene, are associated with a lower likelihood of having exudative AMD. Serum levels of carotenoids were relatively higher in this Chinese cohort than in samples of other ethnicities in previous reports.

Measurement of macular pigment optical density in a healthy Chinese population sample.

PURPOSE Macular pigment may protect against age-related macular degeneration (AMD) by its capacity to absorb blue light and scavenge free radicals. Current information on human macular pigment density has been largely from studies on Caucasian populations. The purpose of this study was to assess macular pigment density and its determinant factors in a Chinese population sample. METHODS Macular pigment optical density (MPOD) was measured in a healthy Chinese population using heterochromatic flicker photometry (HFP). Participants received a standard ophthalmic examination, and only subjects who were confirmed not to have any eye diseases except mild age-related cataract were included in the study. Demographic and lifestyle data and general health status were recorded by questionnaire. RESULTS A total of 281 unrelated healthy Chinese individuals, including 96 males and 185 females, with ages ranging from 17 to 85 years, participated in the study. The mean and standard deviation of MPOD levels were 0.56 ± 0.19, 0.49 ± 0.18, 0.36 ± 0.15, and 0.19 ± 0.12, respectively, at 0.25°, 0.5°, 1.0°, and 1.75° eccentricity points. A significant age-related decline in MPOD was observed at 0.25° (P = 0.014). Females tended to have relatively lower levels of MPOD than males at 0.25° (P = 0.21), 0.5° (P = 0.025), and 1.0° (P = 0.16). No statistically significant association of MPOD was observed with body mass index or smoking status. CONCLUSIONS Macular pigment density measured by HFP tended to decline with aging in this healthy Chinese population sample. Females may have lower levels of MPOD than males.

Relationship of retinal vascular calibre and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus: the Desheng Diabetic Eye Study

Aims To describe the relationship of retinal arteriolar and venular calibre with diabetic retinopathy (DR) and related risk factors, including glucose levels and other biomarkers in a Chinese population with type 2 diabetes mellitus (T2DM). Methods A cross-sectional study. Patients with T2DM were recruited from a local community in urban Beijing. Seven fields 30° colour fundus photographs were taken and examined for the presence and severity of DR using a standardised grading system. Retinal vascular calibres were measured and expressed as average central retinal arteriolar and venular equivalent using a computer-based program. Results A total of 1340 patients with T2DM were included for analysis. Of these, 472 (35.22%) had DR. Wider retinal venular calibre, but not arteriolar calibre, was associated with increasing glucose and glycosylated haemoglobin A1c levels (p<0.006) and dyslipidaemia (p for trend <0.05). After adjusting for possible covariates, the higher quartile of retinal venular calibre was associated with higher prevalence of any DR (OR 2, 95% CI 1.36 to 2.95). Venular calibre increased from 224.33 μm in those without retinopathy to 231.21 μm in those with mild, 241.01 μm in those with moderate and 235.65 μm in those with severe retinopathy (p for trend <0.001). Arteriolar calibre was not associated with DR. Conclusions In the current study, wider venular calibre, but not arteriolar calibre, was shown to be associated with development and increased severity of DR independently from other risk factors in a Chinese diabetic population.

Association of C(-106)T Polymorphism in Aldose Reductase Gene with Diabetic Retinopathy in Chinese Patients with Type 2 Diabetes Mellitus

OBJECTIVE To identify the possible association between C(-106)T polymorphism of the aldose reductase (ALR) gene and diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM). METHODS From November 2009 to September 2010, patients with T2DM were recruited and assigned to DR group or diabetic without retinopathy (DWR) group according to the duration of diabetes and the grading of 7-field fundus color photographs of both eyes. Genotypes of the C(-106)T polymorphism (rs759853) in ALR gene were analyzed using the MassARRAY genotyping system and an association study was performed. RESULTS A total of 268 T2DM patients (129 in the DR group and 139 in the DWR group) were included in this study. No statistically significant differences were observed between the 2 groups in the age of diabetes onset (P=0.10) and gender (P=0.78). The success rate of genotyping for the study subjects was 99.6% (267/268), with one case of failure in the DR group. The frequencies of the T allele in the C(-106)T polymorphism were 16.0% (41/256) in the DR group and 19.4% (54/278) in the DWR group (P=0.36). There was no significant difference in the C(-106)T genotypes between the 2 groups (P=0.40). Compared with the wild-type genotype, odds ratio (OR) for the risk of DR was 0.7 (95% CI, 0.38-1.3) for the heterozygous CT genotype and 0.76 (95% CI, 0.18-3.25) for the homozygous TT genotype. The risk of DR was positively associated with microalbuminuria (OR=4.61; 95% CI, 2.34-9.05) and insulin therapy (OR=3.43; 95% CI, 1.94-6.09). CONCLUSIONS Microalbuminuria and insulin therapy are associated with the risk of DR in Chinese patients with T2DM. C(-106)T polymorphism of the ALR gene may not be significantly associated with DR in Chinese patients with T2DM.

C-reactive protein and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus

AIM To investigate the relationship between C-reactive protein (CRP) and diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM). METHODS Community-based observational cohort study. There were 1131 participants recruited from November 2009 to September 2011 in Desheng community in urban Beijing. Patients diagnosed T2DM were recruited and underwent a standardized evaluation consisting of a questionnaire, ocular and anthropometric examinations and laboratory investigation. The presence and severity of DR were assessed by seven fields 30° color fundus photographs. Subjects were then classified into groups with no DR, any DR, or vision-threatening DR. CRP was analyzed from serum of study subjects. RESULTS A total of 1007 patients with T2DM were included for analysis, including 408 (40.5%) men and 599 (59.5%) women. The median CRP level was 1.5 mg/L for women and 1.1 mg/L for men (P=0.004, OR 0.37, 95% CI 0.18-0.74). After adjusting for possible covariates, higher levels of CRP were associated with lower prevalence of any DR (P=0.02, OR 0.55, 95% CI 0.35-0.89), but not associated with vision-threatening DR (P=0.62, OR 0.78, 95% CI 0.28-2.14). After stratification by sex, the inverse association between CRP and DR was found to be statistically significant in men (P=0.006, OR 0.35, 95% CI 0.16-0.73), but not in women (P=0.58, OR 0.88, 95% CI 0.29-1.16). CONCLUSION The data drawn from a Chinese population with T2DM suggest that increasing CRP levels may be inversely associated with development of DR.

Strategies of Digital Fundus Photography for Screening Diabetic Retinopathy in a Diabetic Population in Urban China

Purpose: To evaluate the effect of mydriasis and different field strategies on technical failure, probability to refer diabetic retinopathy (DR, sensitivity) and probability not to refer patients without DR (specificity) of digital photography in screening with a fundus camera. Methods: A total of 531 patients with diabetes underwent fundus photography with cross-combinations of mydriasis/nonmydriasis and single-field/two-field strategies, followed by slit lamp biomicroscopic examination by a trained ophthalmologist. Fundus photographs were graded independently by another experienced ophthalmologist. Calculations were first based on cases with non-gradable images treated as being referred and then with them excluded. Results: Percentages of DR and referable DR in this patient cohort were 22.4% and 7.7%, respectively, based on slit lamp biomicroscopic examination. Mydriasis significantly reduced the technical failure rate from 27.1% to 8.3% under a single-field strategy, and from 28.2% to 8.9% under a two-field strategy. As compared to the single-field strategy, the two-field strategy increased sensitivity from 75.6% to 87.8% without mydriasis and from 73.2% to 90.2% with mydriasis. Mydriasis increased specificity from 68.8% to 84.3% in the single-field strategy and from 64.7% to 81.6% in the two-field strategy. Had the subjects with non-gradable images been excluded, the two-field strategy without mydriasis reported sensitivity of 85.7% and specificity of 91.6%. Conclusions: Both mydriasis and the two-field strategy are useful in photographic screening tests. Technical failure should be taken into consideration when screening strategies for DR are determined.

The diurnal variation pattern of choroidal thickness in macular region of young healthy female individuals using spectral domain optical coherence tomography.

AIM To investigate the pattern of diurnal variations of choroidal thickness of macular region of healthyindividuals. METHODS A prospective study of 32 healthy female subjects was conducted. Each subject underwent 1) a questionnaire on daily schedule, 2) the Pittsburgh Sleep Quality Index questionnaire (PSQI), and 3) ocular examinations including an eye dominance test, fundus photography, and sequential optical coherence tomography (OCT) imaging, on two separate days at five fixed 3h time intervals. Choroidal thickness was measured by two masked graders. RESULTS A significant diurnal variation of choriodal thickness at fovea (P<0.001), at 500 µm nasal (P<0.001), temporal to fovea (P=0.01) or 1500 µm nasal to fovea (P=0.001) was observed. The median choroidal thickness peaked at 11:00 at fovea (P=0.01), at 500 µm nasal (P=0.009) and temporal (P=0.03) to fovea. The median amplitude of foveal choroidal thickness was 20.5 µm (13, 31) and 20.0 µm (12.5, 28.2) for the first and second series of measurements, respectively. The greater amplitude of foveal choroidal thickness was associated with thickner initial foveal choroidal thickness [0.05 (0.03, 0.08), P=0.01], dominant eye [10.51 (4.02, 14.60), P=0.04] in the multivariate linear regression. CONCLUSION Our data show a significant diurnal variation of the choroidal thickness at fovea, at 500 µm nasal and temporal to fovea and 1500 µm nasal to fovea. Thicker initial foveal choroidal thickness and being dominant eye may influence the amplitude of foveal choroidal thickness.

Inhibition of cell proliferation and migration after HTRA1 knockdown in retinal pigment epithelial cells

PurposeThe purpose of this study was to investigate the role of HtrA serine peptidase 1 (HTRA1) in the proliferation and migration of cells of the human retinal pigment epithelial cell line ARPE-19, and the possible mechanisms involved.MethodsARPE-19 cells were transduced by a recombinant lentiviral vector carrying HTRA1-shRNA to knockdown HTRA1 expression. Subsequent HTRA1 gene and HTRA1 protein levels in these cells and control cells were detected by quantitative real-time PCR and Western blot, respectively. Changes in cell proliferation and migration associated with the inhibition of HTRA1 expression were assessed, as well as changes in the mRNA levels of transforming growth factor beta 1 (TGFB1), bone morphogenetic protein 4 (BMP4), and bone morphogenetic protein 2 (BMP2).ResultsThe recombinant lentivirus carrying HTRA1-shRNA was successfully generated, as evidenced by reduced levels of HTRA1 mRNA and HTRA1 protein in ARPE-19 cells. The knockdown of HTRA1 in ARPE-19 cells was associated with reduced cellular proliferation and migration, and increased mRNA levels of TGF-β1, BMP4, and BMP2.ConclusionsSilence of the HTRA1 gene was associated with significantly higher levels of TGF-β1, BMP4, and BMP2 mRNA and reduction in the proliferation and migration of ARPE-19 cells.

Measurement of macular pigment optical density among healthy Chinese people and patients with early-stage age-related macular degeneration

AIM To measure the macular pigment optical density (MPOD) in healthy Chinese people and patients with early age-related macular degeneration (AMD). METHODS Cross-sectional population based study. Demographic and lifestyle characteristics were ascertained by questionnaire. A food frequency questionnaire was completed for all participants. Participants underwent general physical and ophthalmic examinations and MPOD was measured by heterochromatic flicker photometry. Foveal architecture was measured by optical coherence tomography. RESULTS MPOD of 225 participants (122 healthy and 103 early AMD) was 0.48±0.18. Patients with early AMD (0.52±0.19) tended to have higher MPOD levels than healthy people (0.47±0.17), but the difference was not statistically significant (P=0.06). Participants with carrot or corn oil intake every week tended to have higher levels of MPOD (P=0.002 and 0.008 respectively) while those with corn intake had relatively lower level of MPOD (P=0.01). MPOD increased with the center foveal thickness (P=0.01). CONCLUSION Our findings show that there is no statistically significant association between MPOD and early AMD in the studied population. MPOD is related to center foveal thickness and diets would influence MPOD levels.