Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases

Beijing, China

Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases

Beijing, China

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Jiao J.,Peking University | Jiao J.,Key Laboratory of Vision Loss and Restoration | Jiao J.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases | Jiao J.,Capital Medical University | And 7 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2017

The apelin was reported to be involved in angiogenesis. This study investigated its role in the development of experimental choroidal neovascularization (CNV) model. Lentivirus-mediated short hairpin RNA (shRNA) targeting the rat apelin gene (Apelin-RNAi-LV) and control shRNA (NC-RFP-LV) were designed and employed. Experimental CNV rat models induced by laser photocoagulation were randomly assigned to be intravitreally injected with phosphate-buffered saline (PBS), NC-RFP-LV and Apelin-RNAi-LV. The expression of apelin was evaluated by RT-PCR analysis, western-blot analysis, and immunofluorescence staining. The laser-induced CNV tissue was assessed qualitatively and quantitatively by histopathological sections, fundus fluorescein angiography, and choroidal fl at mounts. The gene expression of apelin was upregulated during CNV formation in a time-dependent manner. By silencing the apelin gene, the expression of apelin was downregulated significantly, and the laser-induced CNV was inhibited obviously. Our study suggests that the apelin may play an important role in the development of laser-induced CNV, and it may act as a novel therapeutic option to inhibit CNV formation.


Cheng Y.,Peking University | Cheng Y.,Key Laboratory of Vision Loss and Restoration | Cheng Y.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases | Qu J.,Peking University | And 11 more authors.
PLoS ONE | Year: 2015

Purpose: Anterior segment neovascularization (ASNV) could be a masquerade for ocular ischemic syndrome (OIS) in diabetic patients which misleads diagnosis and treatment. The purpose of our study is to find the relationship between blood flow velocity in carotid siphon and the development of ASNV in diabetic. Methods: We reviewed 34 eyes of 17 diabetic patients who had Transcranial Color Doppler (TCD) examination with unilateral ASNV. The circulatory parameters of both eyes of each patient were compared and analyzed. In addition, 9 patients with more than 50% stenosis of extracranial internal carotid artery (ICA) and low velocity flow through TCD had been treated by carotid revascularization surgery. Results: The maximal velocity in systole (Vmax) of carotid siphon (SCA) was lower in the eyes with ASNV than in the eyes without ASNV (P<0.05). ASNV of all the 9 patients regressed totally and BCVA improved significantly (P<0.05). Stenosis of ICA and arm-retina time (ART) decreased significantly (P<0.01) and SCA and ophthalmic artery (OA) increased significantly (P<0.01). Conclusions: Our study showed ASNV could be a masquerade for OIS in patients with diabetic retinopathy. The decreased blood flow velocity in carotid siphon is related to the development of ASNV. Circulatory parameters screening of SCA by TCD is important to help us to evaluate the blood flow in SCA, the possibility of development of ASNV, and the prognosis of the patient. Interference such as carotid endarterectomy (CEA) or carotid artery stenting (CAS) can be performed if necessary to improve the blood flow in SCA and make ASNV regression. © 2015 Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Huang L.,Peking University | Huang L.,Key Laboratory of Vision Loss and Restoration | Huang L.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases | Li Y.,Peking Union Medical College | And 28 more authors.
Investigative Ophthalmology and Visual Science | Year: 2014

PURPOSE. To investigate whether 11 variants in complement factor H gene contributed differently in patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) of Chinese descent. METHODS. We performed a case-control study in a group of Chinese patients with nAMD (n = 344) or PCV (n = 368) and contrasted the results against an independent control group comprising 511 mild cataract patients without any evidence of age-related maculopathy. Association analysis of allele and genotype frequencies was performed for 11 haplotypetagging single-nucleotide polymorphisms (SNPs) at the CFH locus (rs1061170, rs1329428, rs1410996, rs2284664, rs375396, rs529825, rs551397, rs7540032, rs800292, rs2274700, and rs1065489). Multinomial logistic regression analyses were performed to estimate and compare the effect of these 11 CFH polymorphisms on AMD and PCV, using the wild-type genotype as reference. Differences in the observed genotypic distributions between cases and controls were tested by using χ2 tests, with age and sex adjusted for using logistic regression. RESULTS. CFH rs1065489 was not significantly associated with the nAMD phenotype in Chinese collections either on univariate or multivariate analysis (P > 0.05 for all comparisons). The other 10 SNPs of CFH were significantly associated with the nAMD phenotype. As for PCV, all 11 SNP markers were significantly associated with risk of PCV before or after correction for age and sex differences. Eight of the 11 SNP markers showed significant evidence of heterogeneity between AMD and PCV (P < 0.05 for all comparisons). CONCLUSIONS. Our data suggest that the genetic architecture at the CFH locus is complex with some markers showing significant skewing of the genotypes toward nAMD or PCV in Asians. This further supports the clinical observation that nAMD and PCV could have distinct pathogenesis mechanisms, which will require larger studies to accurately dissect. © 2014 The Association for Research in Vision and Ophthalmology, Inc.


Li F.,Peking University | Li F.,Key Laboratory of Vision Loss and Restoration | Li F.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases | Li Y.,Peking Union Medical College | And 24 more authors.
Ophthalmic Research | Year: 2014

Purpose: To analyze the association between ABCA1 rs1883025 variants with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in a northern Chinese population. Methods: The study enrolled 900 subjects, including 300 controls, 300 cases with nAMD and 300 cases with PCV. Genomic DNA was extracted from venous blood leukocytes. Single-nucleotide polymorphisms in the ABCA1 (rs1883025) gene were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: The ABCA1 rs1883025 polymorphism was not significantly associated with nAMD (22.5%; p > 0.05) or PCV (20.8%; p > 0.05) in a northern Chinese population. The association remained insignificant after adjustment for age and gender differences (p > 0.05). Conclusions: This study suggests that ABCA1 rs1883025 variants are not associated with nAMD or PCV in a Chinese population, which is likely due to an ethnic difference. © 2014 S. Karger AG, Basel.


Cheng Y.,Peking University | Cheng Y.,Key Laboratory of Vision Loss and Restoration | Cheng Y.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases | Shi X.,Peking University | And 11 more authors.
Chinese Medical Journal | Year: 2016

Background: Polypoidal choroidal vasculopathy (PCV) is characterized by the presence of polyps with or without a branching vascular network and more prevalent among Asians. The aim of this study was to compare the outcomes of conbercept therapy between two different angiographic subtypes of PCV. Methods: Fifty-eight patients of PCV were classified into two phenotypes according to indocyanine green angiography (ICGA). In Type 1,both feeder and draining vessels are visible on ICGA and network vessels are numerous. In Type 2,neither feeder nor draining vessels are detectable,and the number of network vessels is small. The patients were treated with intravitreal conbercept (IVC) for 3 months.additional IVC was given at subsequent monthly visits,if needed. The patients were followed up for 12 months,and changes in mean best-corrected visual acuity (BCVA),central retinal thickness (CRT),subretinal fluid (SRF) thickness,pigmented epithelial detachment (PED),hemorrhage,and number of polypoidal lesions were evaluated. Results: The mean BCVA in Type 2 PCV (15.92 ± 9.76 letters) achieved a significantly greater improvement than that in the Type 1 (14.10 ± 9.07 letters) at month 12 (t = 2.37,P < 0.01). Moreover,the mean CRT decrease was numerically greater in Type 2 (120.44 ± 73.81 µm) compared with Type 1 (106.48 ± 72.33 µm) at month 6 (t = 4.31,P < 0.01),and greater in Type 2 (130.21 ± 76.28 µm) compared with Type 1 (111.67 ± 79.57 µm) at month 9 (t = 1.87,P < 0.01). There was no significant difference between the two types for the decrease in SRF thickness,PED height,and regression of polyps from month 3 to 12 (t = 2.97,P > 0.05). Conclusion: Classification systems for PCV will show differences in presentation,natural history,or response to anti-vascular endothelial growth factor treatment and might,therefore,provide a new key to the choice of treatment for the disease. © 2016 Chinese Medical Journal.


Wen J.,Peking University | Wen J.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases | Jiang Y.,Peking University | Jiang Y.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases | And 4 more authors.
British Journal of Ophthalmology | Year: 2015

Background/Aims: This study evaluated the impact of intravitreal injection of bevacizumab (IVB) on the microenvironment of the eyes of diabetic macular oedema (DMO) and macular oedema due to central retinal vein occlusion (CRVO-MO) patients. Methods: This study comprised 136 patients, including 51 patients in the DMO group, 70 in the CRVO-MO group and 15 in the control group, who were followed for 6 months after IVB. Angiogenic cytokines, inflammatory cytokines and growth factors concentrations in the aqueous humour were measured before and after IVB using suspension array technology. We compared the levels of cytokines among DMO patients, CRVO-MO patients and control patients. We compared the levels of cytokines among groups according to the interval between the first and second injections of bevacizumab and according to the number of injections received during the 6-month follow-up period. Results: Significantly higher concentrations of vascular endothelial growth factor (VEGF), transforming growth factor β (TGF-β), hepatocyte growth factor (HGF), interleukin 6 (IL-6), serum amyloid A (SAA) and monocyte chemoattractant protein-1 (MCP-1) were found in the aqueous humour of DMO and CRVO-MO patients compared with cataract patients. One month after IVB, the intraocular concentrations of VEGF were significantly decreased in the eyes of DMO ( p=0.045) and CRVO-MO (p=0.002) patients compared with baseline. No other cytokine was significantly altered by bevacizumab therapy. Conclusions: Angiogenic, inflammatory and growth factors are involved in the development of DMO and CRVO-MO. In addition to VEGF, IVB did not cause significant differences in other inflammatory cytokines and growth factors in DMO and CRVO-MO patients.


Meng Q.,Peking University | Meng Q.,Key Laboratory of Vision Loss and Restoration | Meng Q.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases | Huang L.,Peking University | And 20 more authors.
PLoS ONE | Year: 2015

Purpose To investigate the effect of genetic variants in the high-density lipoprotein (HDL) metabolic pathway and risk factors on neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in China. Methods A total of 742 Chinese subjects, including 221 controls, 230 cases with nAMD, and 291 cases with PCV, were included in the present study. Five single nucleotide polymorphisms (SNPs) from three genes in the HDL metabolic pathway (HDLMP) including cholesteryl ester transfer protein (CETP), hepatic lipase (LIPC) and lipoprotein lipase (LPL) were genotyped in all study subjects with matrix-Assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Risk factors including gender, hypertension, hyperlipidemia, diabetes mellitus, and coronary artery disease were identified. Chi-square tests or Fisher's exact tests were applied to discover associations between SNPs and risk factors for PCV and nAMD. Gene-gene interactions and gene-environment interactions were evaluated by the multifactor-dimensionality reduction (MDR) method. Results CETP rs3764261 were significantly associated with an increased risk for PCV (odds ratio (OR) = 1.444, P = 0.0247). LIPC rs1532085 conferred an increased risk for PCV (OR = 1.393, P = 0.0094). We found no association between PCV and LPL rs12678919, LIPC rs10468017 or CETP rs173539. No association was found between five SNPs with nAMD. Regarding risk factors, females were found to have significantly decreased risks for both PCV and nAMD (P = 0.006 and 0.001, respectively). Coronary artery disease (CAD) was a risk factor in PCV patients but played a protective role in nAMD patients. Hyperlipidemia was associated with PCV but not with nAMD. Neither hypertension nor diabetes mellitus was associated with PCV or nAMD. The MDR analysis revealed that a three-locus model with rs12678919, rs1532085, and gender was the best model for nAMD, while a five-locus model consisting of rs10468017, rs3764261, rs1532085, gender, and hyperlipidemia was best for PCV. Conclusion Our large-sample study suggested that CETP rs3764261 conferred an increased risk for PCV. We also first found the association between rs1532085 and PCV. The result of present study also showed that gender and CAD are associated with PCV and nAMD. Significant association was found between hyperlipidemia and PCV but not nAMD. © 2015 Meng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Li F.,Peking University | Li F.,Key Laboratory of Vision Loss and Restoration | Li F.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases | Bai Y.,Peking University | And 17 more authors.
Ophthalmic Research | Year: 2015

Purpose: The aim of this study was to investigate the effects of quercetin on vascular endothelial growth factor (VEGF)-induced choroidal and retinal angiogenesis in vitro using a rhesus macaque choroid-retinal endothelial (RF/6A) cell line. Methods: RF/6A cells were cultured in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum. Then the cells were treated with different concentrations (from 0 to 100 μM) of quercetin and 100 ng/ml VEGF. The cell proliferation was assessed using cholecystokinin octapeptide dye. The cell migration was investigated by a Transwell assay. The tube formation was measured on Matrigel. Furthermore, the impact of quercetin's effects on VEGF-induced activation of VEGF receptor 2 (VEGFR-2) downstream signal pathways was tested by Western blot analysis. Results: Quercetin inhibits RF/6A cell proliferation in a dose-dependent fashion: 22.7, 31.5 and 36.7% inhibition on treatment with 10, 50 and 100 μM quercetin, respectively. VEGF-induced migration and tube formation of RF/6A cells were also significantly inhibited by quercetin in a dose-dependent manner. Quercetin inhibits VEGF-induced VEGFR-2 downstream signal pathways of RF/6A. Conclusions: The results show that quercetin inhibits VEGF-induced cell proliferation, migration and tube formation of RF/6A. We suggest that quercetin inhibits VEGF-induced choroidal and retinal angiogenesis in vitro. Collectively, the findings in the present study suggest that quercetin inhibits VEGF-induced choroidal and retinal angiogenesis by targeting the VEGFR-2 pathway. This suggests that quercetin is a choroidal and retinal angiogenesis inhibitor. © 2015 S. Karger AG, Basel.


Li S.,Peking University | Li S.,Key Laboratory of Vision Loss and Restoration | Li S.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases | Huang L.,Peking University | And 27 more authors.
Investigative Ophthalmology and Visual Science | Year: 2015

PURPOSE. Recent research has provided novel but contrary insight into the function of Slit2- Robo signaling in angiogenesis. Although the role of Robo in choroidal neovascularization (CNV) has been studied, the effect of its ligand, Slit2, on CNV development is unclear. This study investigated the role of endogenous Slit2 in CNV and the possible mechanisms. METHODS. Laser-induced CNV in Slit2 transgenic and wild-type mice was used to study the effects of endogenous Slit2 on angiogenesis in vivo. Fluorescein angiography was performed to evaluate the leakage area of each lesion. Plasmid-based gene transfer technology was used to increase Slit2 expression and to study its effects on human umbilical vein endothelial cells (HUVECs) in vitro. Cell proliferation, migration, and tube formation were assessed. Quantitative real-time PCR and Western blot were used to measure expression in the extracellular signal-related kinase 1/2 (ERK1/2), protein kinase B (AKT), and p38 mitogen- activated protein kinase (p38 MAPK) molecular pathways. RESULTS. Laser treatment led to more CNV and vascular leakage in Slit2 transgenic mice compared with wild-type mice. Upregulation of Slit2, Robo1, VEGF receptor 2 (VEGFR2), and phosphorylated ERK1/2 (p-ERK1/2) were detected in retina and choroidal tissue of laser- treated transgenic mice. After transfection of HUVECs with a Slit2 overexpression plasmid, cell proliferation, migration, and tube formation capacities were promoted. Slit2, Robo1, VEGFR2, and p-ERK1/2 were elevated in transfected HUVECs. CONCLUSION. Slit2 overexpression promoted angiogenic effects in both a laser-induced CNV mouse model and HUVECs and promoted the biological activity of endothelial cells. Slit2 may promote angiogenesis by upregulating Robo1 and activating the VEGFR2-ERK1/2 pathway. © 2015 The Association for Research in Vision and Ophthalmology, Inc.


Li T.,Peking University | Li T.,Key Laboratory of Vision Loss and Restoration | Li T.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases | Meng Q.,Peking University | And 14 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2016

In order to identify the spectrum of RB1 gene mutation in Chinese retinoblastoma (RB) patients, a total of 38 RB patients, including 15 bilateral cases and 23 unilateral cases were included in this study. DNA samples were extracted from patients' peripheral blood and we performed PCR direct sequencing of the promoter and the 27 coding exons of the RB1 gene to screen RB1 mutation. In total, we identified nine causative RB1 mutations in ten of 38 RB patients, and the global mutation rate is 26.3%. Five mutations have not been reported previously, including 1 nonsense mutation (p.169Cys > Term), 2 small deletions of one two base pairs (c.2047delC and c.871-872delGT) and 2 missense mutations (p.470Ile > Phe and p.Val654Leu). The other four mutations include 2 nonsense mutations (p.344Gln > Term and p.685Gln > Term), 1 small deletion of 2 base pair causing a frameshift and premature termination (c.371-372delTA) and 1 nonsense mutation (p.Gln344Ter). We reported 5 novel germline RB1 mutations in Chinese RB patients in this study. Our results make contributions to the molecular diagnosis, risk prediction and early management in the proband and extended family.

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