[Show abstract][Hide abstract] ABSTRACT: Background:
A traditional Chinese medicine, Tetramethylpyrazine (TMP), has been prescribed as a complementary treatment for glaucoma to improve patient prognosis. However, the pharmacological mechanism of action of TMP is poorly understood. In previous studies, we demonstrated that TMP exerts potent inhibitory effects on neovascularization, suppresses the tumorigenic behavior of glioma cells, and protects neural cells by regulating CXCR4 expression. Here, we further investigated whether the SDF-1/CXCR4 pathway is also involved in the TMP-mediated activity in trabecular meshwork cells.
CXCR4 expression was examined by quantitative real-time PCR in trabecular and iris specimens from 54 primary open-angle glaucoma (POAG) patients who required surgery and 19 non-glaucomatous donors. Our data revealed markedly elevated CXCR4 expression in the trabecular meshwork of POAG patients compared with that of controls. Consistently, CXCR4 expression was much higher in glaucomatous trabecular meshwork cells than in normal trabecular meshwork cells. Using RT-PCR and western blot assays, we determined that glaucoma-related cytokines and dexamethasone (DEX) also significantly up-regulated CXCR4 expression in primary human trabecular meshwork (PHTM) cells. Moreover, the TGF-β1-mediated induction of CXCR4 expression in PHTM cells was markedly down-regulated by TMP compared with control treatment (PBS) and the CXCR4 antagonist AMD3100. In addition, TMP could counteract the TGF-β1-induced effects on stress fiber accumulation and expansion of PHTM cells. TMP markedly suppressed the migration of PHTM cells stimulated by TGF-β1 in transwell and scratch wound assays. TMP also suppressed the extracellular matrix (ECM) accumulation induced by TGF-β2.
Our findings demonstrate that CXCR4 might be involved in the pathogenetic changes in the trabecular meshwork of patients with POAG. Additionally, TMP might exert its beneficial effects in POAG patients by down-regulating CXCR4 expression.
PLoS ONE 08/2015; 10(8):e0133055. DOI:10.1371/journal.pone.0133055 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate the intermediate surgical results of Ahmed glaucoma valve (AGV) implantation in patients less than 7 years of age, with advanced primary congenital glaucoma who have failed previous surgeries.
Consecutive patients with advanced primary congenital glaucoma that failed previous operations and had undergone subsequent AGV implantation were evaluated retrospectively. Surgical success was defined as 1) intraocular pressure (IOP) ≥6 and ≤21 mmHg; 2) IOP reduction of at least 30% relative to preoperative values; and 3) without the need for additional surgical intervention for IOP control, loss of light perception, or serious complications.
Fourteen eyes of eleven patients were studied. Preoperatively, the average axial length was 27.71±1.52 (25.56-30.80) mm, corneal diameter was 14.71±1.07 (13.0-16.0) mm, cup-to-disc ratio was 0.95±0.04 (0.9-1.0), and IOP was 39.5±5.7 (30-55) mmHg. The mean follow-up time was 18.29±10.96 (5-44, median 18) months. There were significant reductions in IOPs and the number of glaucoma medications (P<0.001) postoperatively. The IOPs after operation were 11.3±3.4, 13.6±5.1, 16.3±2.7, and 16.1±2.6 mmHg at 1 month, 6 months, 12 months, and 18 months, respectively. Kaplan-Meier estimates of the cumulative probability of valve success were 85.7%, 71.4%, and 71.4% at 6, 12, and 18 months, respectively. Severe surgical complications, including erosion of tube, endophthalmitis, retinal detachment, choroidal detachment, and delayed suprachoroidal hemorrhage, occurred in 28.6% cases.
AGV implantation remains a viable option for patients with advanced primary congenital glaucoma unresponsive to previous surgical intervention, despite a relatively high incidence of severe surgical complications.
[Show abstract][Hide abstract] ABSTRACT: Evidence-based medicine (EBM) has markedly promoted the development of ophthalmology.Glaucoma clinical trials have been developed rapidly. Clinical trial papers have been tremendously increasing in the decade, but unhealthy tendency deviating from the nature of EBM---"conscientious, explicit and judicious" has come into notice by the medical society. It is the time to develop patient based medicine, combining with experience-based, experiment-based, ethics-based, economy-based medicine. Only face up to the fundamental problems can we avoid misleading clinicians and provide better health care of affordable, accessible, accountable medical service for patients. This is the intrinsic value of evidence-based medicine.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 02/2015; 51(2):84-5. DOI:10.3760/cma.j.issn.0412-1081.2015.02.002
[Show abstract][Hide abstract] ABSTRACT: To confirm the non-inferiority of the IOP-lowering effect of the 0.0015% Tafluprost ophthalmic solution to the 0.005% Latanoprost ophthalmic solution in patients with primary open-angle glaucoma or ocular hypertension.Safety was also compared between two groups.
This study was conducted from August 2008 to December 2009, at five clinical trial sites in China. Patients of this study population was diagnosed with primary open-angle glaucoma or ocular hypertension in both eyes.Subjects were randomized into 0.0015% Tafluprost group or 0.005% Latanoprost group.Intraocular pressure (IOP) measurement by Goldmann applanation tonometer, slit-lamp microscopy, Gonioscopy, Fundascopy, Visual acuity test, Perimetry, Blood pressure and pulse rate, Subjective symptoms were compered between two groups at Week 0, Week 2 and Week 4.For main effectiveness evaluation index adopt the bad effect evaluation, safety evaluation index by Fisher's exact test probability method.
The 246 subjects/246 eyes were randomized (Tafluprost group:122 subjects/122 eyes, Latanoprost group:124 subjects/ 124 eyes). Change in the IOP at 17:00 of Week 2 is (8.8 ± 3.8) mmHg and (8.9 ± 4.4) mmHg (1 mmHg = 0.133 kPa) in Tafluprost group and Latanoprost group. Percent change in the IOP at 17:00 of Week 2 is (33.2 ± 12.8)% and (34.4 ± 14.1)% in Tafluprost group and Latanoprost group. Change in the IOP at 17:00 at the end of treatment is (9.8 ± 4.0) mmHg and (9.2 ± 4.1) mmHg in Tafluprost group and Latanoprost group. Percent change in the IOP at 17:00 at the end of treatment is 37.2% ± 13.4% group and 35.7% ± 13.0% in Tafluprost and Latanoprost group.In addition, distribution of subjects with percentage decrease of IOP > 30% was 72.5% in Tafluprost group higher than 63.8% in Latanoprost group. The major adverse reactions were conjunctival hyperemia, eye irritation, eye pain and foreign body sensation. The incidence of adverse reactions is 31.7% in Tafluprost group and 20.8% in Latanoprost group. The inter-group difference had no statistical significance.
Efficacy and safety of Tafluprost ophthalmic solution are no less than Latanoprost ophthalmic solution in patients with primary open-angle glaucoma or ocular hypertension.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 02/2015; 51(2):95-102. DOI:10.3760/cma.j.issn.0412-1081.2015.02.007
[Show abstract][Hide abstract] ABSTRACT: In this study, we utilized yellow-wavelength laser treatment and measured aqueous outflow facility to establish a model for chronic glaucoma in rhesus monkeys. We then compared the effects of photocoagulation resulting from exposure to the yellow laser or to a green laser. Twelve rhesus monkeys were used to establish the model, and the yellow and green lasers were utilized for 360° photocoagulation in the anterior-chamber angles of the right eye in all subjects. After certain periods of time before and after the creation of the glaucoma model, the cornea, aqueous humor, optic cup, intraocular pressure (IOP), outflow facility, retinal nerve fiber layer (RNFL), and pathology of the trabecular meshwork were analyzed. Both the yellow and green lasers caused an increase in IOP compared with before photocoagulation (18.6 ± 2.6 mm Hg and 16.1 ± 1.8 mm Hg, respectively), with an average photocoagulation from the yellow and green lasers of 39.2 ± 7.9 mm Hg and 30.3 ± 4.7 mm Hg, respectively (P < 0.01). However, the success rate of a second photocoagulation treatment in the yellow laser group was significantly higher than in the green laser group (P < 0.05). After the increase in IOP, both groups exhibited an inflammatory response in the anterior segment, enlarged cupping, and a decrease in the average thickness of the RNFL. However, the yellow laser caused less corneal edema than the green laser (P < 0.05), and the outflow facility of the two groups (0.33 ± 0.09 and 0.30 ± 0.07 μl/min/mm Hg for the yellow and green lasers, respectively) showed different degrees of differences (0.05 ± 0.02 and 0.07 ± 0.02 μl/min/mm Hg for the yellow and green lasers, respectively) into the abnormal range after photocoagulation. Pathological examination revealed that the depth of destruction of the trabecular meshwork appeared to be deeper in the yellow laser group than in the green laser group. In conclusion, application of a yellow laser combined with measuring aqueous outflow facility produced a glaucoma model with a minor inflammatory response and few IOP fluctuations.
Experimental Eye Research 12/2014; 131. DOI:10.1016/j.exer.2014.12.012 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
The purpose of this study is to evaluate the functional and morphological changes in subretinal xenografts of human retinal progenitor cells (hRPCs) in B6 mice treated with Cyclosporin A (CsA; 210 mg/l in drinking water).
The hRPCs from human fetal eyes were isolated and expanded for transplantation. These cells, with green fluorescent protein (GFP) at 11 passages, were transplanted into the subretinal space in B6 mice. A combination of invasive and noninvasive approaches was used to analyze the structural and functional consequences of the subretinal injection of the hRPCs. The process of change was monitored using spectral domain optical coherence tomography (SDOCT), histology, and electroretinography (ERG) at 3 days, 1 week, and 3 weeks after transplantation. Cell counts were used to evaluate the survival rate with a confocal microscope. ERGs were performed to evaluate the physiologic changes, and the structural changes were evaluated using SDOCT and histological examination.
The results of the histological examination showed that the hRPCs gained a better survival rate in the mice treated with CsA. The SDOCT showed that the bleb size of the retinal detachment was significantly decreased, and the retinal reattachment was nearly complete by 3 weeks. The ERG response amplitudes in the CsA group were less decreased after the injection, when compared with the control group, in the dark-adapted and light-adapted conditions. However, the cone-mediated function in both groups was less affected by the transplantation after 3 weeks than the rod-mediated function.
Although significant functional and structural recovery was observed after the subretinal injection of the hRPCs, the effectiveness of CsA in xenotransplantation may be a novel and potential approach for increasing retinal progenitor cell survival.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Oxidative stress plays an important role in health and aging. We have shown that oxidative stress impairs mitochondrial function and promotes RPE cell death in an age-dependent manner. This study investigates the role of pigment epithelium-derived factor (PEDF) in limiting oxidative stress-induced damage to RPE cells through mitochondrial pathways.
Three groups of early-passaged RPE cells from donors 50 to 55, 60 to 65, and 70 to 75 years old (yo) were either preconditioned with PEDF followed by exposure to sublethal doses of hydrogen peroxide (H2O2) or post-treated with PEDF after H2O2 treatment. Effects of PEDF on mitochondrial function and cell viability were examined.
Oxidative stress induced an age-dependent increase in LDH release, reactive oxygen species (ROS) levels, and cell death and a decrease in adenosine triphosphate (ATP) production and mitochondrial membrane potential (ΔΨm) in human RPE cells. Preconditioning or poststressed treatment with PEDF resulted in increased cell viability, inhibition of cytochrome c release and caspase 3 cleavage, and improved mitochondria function denoted by a decrease in ROS generation and increases in ATP production and ΔΨm. Oxidative stress also disrupted the reticular network, trafficking, and distribution of the mitochondria and blocked activation of phosphatidylinositol 3 kinase (PI3K), Akt, and Erk signaling in the cells. These effects were more pronounced in RPE cells from individuals>60 yo compared to the 50 to 55 yo age group. Pigment epithelium-derived factor mitigated negative effects of oxidative stress on mitochondrial remodeling and cellular distribution and unblocked its control of PI3K/Akt and mitogen-activated protein kinase (MAPK) signaling. Although PEDF potentiated both PI3K/Akt and MAPK signaling in the cells, stabilization of mitochondrial networks and function was dependent on its activation of PI3K/Akt. Specificity of PEDF's activity was confirmed using the pharmacological inhibitors LY294002, SH6, and U0126. We also show that in the absence of oxidative stress, pharmacological inhibition of the PI3K/Akt pathway alone was sufficient to disrupt mitochondrial structure and function. In addition, PEDF blocked effects of oxidative stress on expression of cyclophilin D and UCP2, genes controlling mitochondrial function, and the apoptotic genes caspase 3, Bax, and Bcl2. Control of ROS levels by PEDF was specifically linked to UCP2 regulation since PEDF-induced expression of this gene in UCP2-deficient cells was associated with a decrease in ROS production.
We provide evidence that PEDF promotes resilience of aging RPE cells to oxidative stress by stabilizing mitochondrial networks and function and that mitochondrial dynamics in human RPE cells are controlled, in part, through the PI3K/Akt pathway.
[Show abstract][Hide abstract] ABSTRACT: Acute glaucoma is a sight-threatening condition characterized by a sudden and substantial rise in intraocular pressure (IOP) and consequent retinal ganglion cell (RGC) death. Angle closure glaucoma, a common cause of glaucoma in Asia that affects tens of millions of people worldwide, often presents acutely with loss of vision, pain, and high IOP. Even when medical and surgical treatment is available, acute angle closure glaucoma can cause permanent and irreversible loss of vision. Toll-like receptor 4 (TLR4) signaling has been previously implicated in the pathogenesis of IOP-induced RGC death, although the underlying mechanisms are largely unknown. In the present study, we used an acute IOP elevation/glaucoma model to investigate the underlying mechanism of RGC death. We found that TLR4 leads to increased caspase-8 expression; this elevation increases IL-1β expression and RGC death via a caspase-1-dependent pathway involving Nod-like receptor family, pyrin domain containing 1 (NLRP1)/NLRP3 inflammasomes and a caspase-1-independent pathway. We show that inhibition of caspase-8 activation significantly attenuates RGC death by down-regulating the activation of NLRP1 and NLRP3, thus demonstrating the pivotal role of caspase-8 in the TLR4-mediated activation of inflammasomes. These findings demonstrate collectively a critical role of caspase-8 in transducing TLR4-mediated IL-1β production and RGC death and highlight signal transduction in a caspase-1-dependent NLRP1/NLRP3 inflammasome pathway and a caspase-1-independent pathway in acute glaucoma. These results provide new insight into the pathogenesis of glaucoma and point to a treatment strategy.
Proceedings of the National Academy of Sciences 07/2014; 111(30). DOI:10.1073/pnas.1402819111 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, a biodegradable thermo-sensitive hydrogel from poly(trimethylene carbonate)15-F127-poly(trimethylene carbonate)15 (PTMC15-F127-PTMC15) was designed and evaluated as an injectable implant during ocular glaucoma filtration surgery in vivo and in vitro. Mitomycin C (MMC) was loaded into this hydrogel for controlled released to prolong the efficacy and to reduce the long-term toxicity. The properties of the hydrogel were confirmed using 1H NMR and gel permeation chromatography (GPC). Compared to the Pluronic F127 hydrogel, the PTMC15-F127-PTMC15 hydrogel showed a good solution-gel transition temperature at 37°C, a lower work concentration of 5% w/v and a longer mass loss time of more than 2 weeks. The in vitro study showed that the drug could be released from PTMC15-F127-PTMC15 (5% w/v) hydrogel for up to 16 days with only 57% of drug released in the first day. Moreover, the cell toxicity, which was tested via LDH and ANNEXIN V/PI, decreased within 72 h in human tenon's fibroblast cells (HTFs). The in vivo behavior in a rabbit glaucoma filtration surgery model indicated that this hydrogel loaded with 0.1 mg/ml MMC led to a better functional bleb with a prolonged mean bleb survival time (25.5±2.9 days). The scar tissue formation, new collagen deposition and myofibroblast generation appeared to be reduced upon histological and immunohistochemistry examinations, with no obvious side effects and inflammatory reactions. The in vitro and in vivo results demonstrated that this novel hydrogel is a safe and effective drug delivery candidate in ocular glaucoma surgery.
PLoS ONE 06/2014; 9(6):e100632. DOI:10.1371/journal.pone.0100632 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Retinal post-mitotic neurocytes display genomic instability after damage induced by physiological or pathological factors. The involvement of BRCA1, an important factor in development and DNA repair in mature retinal neurocytes remains unclear. Thus, we investigated the developmental expression profile of BRCA1 in the retina and defined the role of BRCA1 in DNA repair in retinal neurocytes. Our data show the expression of BRCA1 is developmentally down-regulated in the retinas of mice after birth. Similarly, BRCA1 is down-regulated after differentiation induced by TSA in retinal precursor cells. An end-joining activity assay and DNA fragmentation analysis indicated that the DNA repair capacity is significantly reduced. Moreover, DNA damage in differentiated cells or cells in which BRCA1 is silenced by siRNA interference is more extensive than that in precursor cells subjected to ionizing radiation. To further investigate non-homologous end joining (NHEJ), the major repair pathway in non-divided neurons, we utilized an NHEJ substrate (pEPI-NHEJ) in which double strand breaks are generated by I-SceI. Our data showed that differentiation and the down-regulation of BRCA1 respectively result in a 2.39-fold and 1.68-fold reduction in the total NHEJ frequency compared with that in cells with normal BRCA1. Furthermore, the analysis of NHEJ repair junctions of the plasmid substrate indicated that BRCA1 is involved in the fidelity of NHEJ. In addition, as expected, the down-regulation of BRCA1 significantly inhibits the viability of retina precursor cells. Therefore, our data suggest that BRCA1 plays a critical role in retinal development and repairs DNA damage of mature retina neurocytes.
PLoS ONE 06/2014; 9(6):e99371. DOI:10.1371/journal.pone.0099371 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The aim of this study is to investigate whether CS-g-MMCs conjugate (CSM) could be a new agent to prevent the post-operative fibrosis in a rabbit model of experimental glaucoma filtration surgery.
Materials and methods:
In a randomized, controlled, masked-observer study, 40 New Zealand White rabbits underwent trabeculectomy in the right eyes and randomly received subconjunctival injection of phosphate buffered saline, chitosan (CS), CSM (100 µg/ml), CSM (200 µg/ml) or Mitomycin C (100 µg/ml). Bleb characteristics and anterior chamber depth were evaluated by slit-lamp examination. The animals were killed on day 14 and 28. Histopathology and immunohistochemistry were performed to determine the amount of the scarring and fibrosis. Ocular toxicity was assessed by histopathology and electron microscope.
We found that the five groups were similar with respect to intraocular pressure and anterior chamber depth. The medians for survival days were: 5.5, 8, 17.5, 28 and 16 in the PBS, CS, CSM100, CSM200 and MMC groups, respectively. Both the CSM200 and the MMC group showed a significantly larger bleb area than the CSM100, CS and the PBS group. Less scarring was seen on day 14 and 28 in CSM200 and MMC group than in the PBS, CS and CSM100 group by histology and immunohistochemistry assessment. No damages were found in the rabbit eyes in each group.
Subconjunctival injection of CSM postoperatively can improve the filtration bleb survival in the rabbit model. It can be a safe and effective antimetabolite in glaucoma surgery.
Current eye research 04/2014; 39(10). DOI:10.3109/02713683.2014.894079 · 1.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the power of the 4 intraocular pressure (IOP) measures, that is, peak, mean, range, and SD, over a 24-hour period in predicting IOP variations in order to determine which measure of IOP fluctuation correlates best with actual office-hour readings in glaucoma patients and healthy subjects.
For this prospective study, 25 subjects with untreated primary open-angle glaucoma and 33 healthy individuals were hospitalized for 24 hours. Measurements of the subjects' IOP for both eyes were recorded with a Goldmann applanation tonometer every 3 hours in the sitting position during the daytime (9 AM to 9 PM) and with a TonoPen in both the sitting and supine positions for 24 hours. Only 1 eye was selected randomly per subject for the final analysis. The strength of association between the estimated values and the actual 24-hour IOP data in habitual body positions was analyzed using the coefficient of determination (R). The differences were calculated. The percentage of subjects with estimated IOP values falling within the cutoff values from the 24-hour data were assessed.
The peak IOP was captured outside office hours in 57% of the young subjects, 75% in the elderly control group, and 52% of the glaucoma patients. The estimation of the strength of association for the mean IOP and peak IOP showed strong to moderate correlations (R range from 0.29 to 0.95) compared with the estimation of range and SD of IOP fluctuation, which demonstrated weak to moderate relationships (R range from 0.001 to 0.69). The percentage of significant cases mostly corresponded with the correlation.
With the combination of sitting and supine position readings during office hours, the study provides promising results in estimating the mean and peak IOP in glaucoma patients and healthy subjects; however, it showed little advantage in range and SD of IOP fluctuation.
Journal of glaucoma 04/2014; Publish Ahead of Print(7). DOI:10.1097/IJG.0000000000000059 · 2.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endoplasmic reticulum (ER) stress has been implicated in various neurodegenerative diseases, including Alzheimer's disease. We have previously observed amyloid production in the retina of the Tg2576 transgenic mouse model of Alzheimer's disease. In this study, we used tunicamycin-induced ER stress in RGC-5 cells, a cell line identical to the photoreceptor cell line 661W, to investigate the effect of ER stress on production of amyloid-beta (Abeta) peptides. We found that the mRNA level of amyloid-beta precursor protein (APP) remained stable, while the protein level of amyloid-beta precursor protein (APP) was decreased, the amyloid-beta precursor protein cleaving enzymes beta-site APP-cleaving enzyme 1 and presenilin 1 were upregulated, Abeta1-40 and Abeta1-42 production were increased, and reactive oxygen species production and apoptosis markers were elevated following induction of ER stress. The protein level of Abeta degradation enzymes, neprilysin, endothelin-converting enzyme 1, and endothelin-converting enzyme 2 remained unchanged during the prolonged ER stress, showing that the generation of Abeta did not result from reduction of proteolysis by these enzymes. Inclusion of group II caspase inhibitor, Z-DEVD-FMK, increased the ER stress mediated Abeta production, suggesting that they are generated by a caspase-independent mechanism. Our findings provided evidence of a role of ER stress in Abeta peptide overproduction and apoptotic pathway activation in RGC-5 cells.
[Show abstract][Hide abstract] ABSTRACT: Objective:
To investigate the morphological and functional changes of the laser-induced choroidal neovascularization (CNV) in rhesus monkeys.
Experimental study. Eight adult rhesus monkeys weighted 4 to 7 kg were used in this study. CNVs were induced with small high-energy laser spots at short pulse duration by an argon green laser. Eyes were monitored weekly by color fundus photography, fluorescence fundus angiography (FFA) , and optical coherence tomography (OCT) . Fluorescein leaking intensities of grade 4 CNV lesions were analyzed by the method of ANOVA for repeated measures. Electroretinogram (ERG) was performed before laser photocoagulation and 56 days after laser photocoagulation and the data were analyzed with paired t-test.
(1) FFA revealed that the mean intensities of grade 4 CNV lesions were 89.44 ± 26.28, 97.56 ± 26.47, 110.22 ± 29.76, 100.26 ± 29.24, 91.77 ± 28.11, 77.76 ± 24.85 and 63.23 ± 22.34 on day 14, day 21, day 28, day 35, day 42, day 49, and day 56 respectively and the differences were statistically significant (F = 39.715, P < 0.01) . The differences between any time-point and its previous time-point were also statistically significant (t14-21 = 4.824, P < 0.01; t21-28 = 5.225, P < 0.01; t28-35 = 7.378, P < 0.01;t35-42 = 2.954, P < 0.05; t42-49 = 5.386, P < 0.01; t49-56 = 6.138, P < 0.01). (2) OCT images showed retinal edema, subretinal fluid and hyper-reflective lesions of CNVs in the laser sites and histopathology showed that fibrovascular tissues together with proliferating retinal pigment epithelium cells were seen in the laser sites. (3) ERG data revealed that implicit time of dark-adapted b wave (t = 4.23, P < 0.01) increased while the amplitudes of dark-adapted a wave (t = 6.35, P < 0.01) , dark-adapted b wave (t = 3.12, P < 0.01) and light-adapted b wave (t = 3.93, P < 0.01) decreased 56 days after laser photocoagulation compared with those before laser photocoagulation.
The laser-induced CNV in non-human primate model shows continuous leakage on FFA examination and reduced amplitudes as well as increased implicit time on ERG examination, suggesting that laser-induced CNV primate model not only could be used to study the pathogenesis of CNV formation but also could be used for screening of drug effectiveness.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 03/2014; 50(3):203-8. DOI:10.3760/cma.j.issn.0412-4081.2014.03.010
[Show abstract][Hide abstract] ABSTRACT: Objective:
To investigate the prevalence of blindness and moderate and severe visual impairment among adults aged 50 years or above in Yangxi County of Guangdong Province, China.
It was a population-based cross-section study.Geographically defined cluster sampling was used in randomly selecting 5 531 individuals aged 50 years or above in Yangxi County from September 2006 to January 2007. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. All participants were enumerated using village registers followed by door-to-door visits.Eligible individuals were invited to receive visual acuity measurement and eye examination.Statistical analyses were performed using Stata/SE Statistical Software, release 9.0. Chi-square test was used to investigate the association of age, gender and education with presenting and best corrected visual acuity.
Five thousands five hundreds and thirty-one individuals were enumerated and 4 589 persons were examined, the response rate was 82.97%. Based on the criteria of World Health Organization visual impairment classification in 1973, the prevalence of blindness and moderate and severe visual impairment defined as best corrected visual acuity was 2.38% (109/4 589) and 9.44% (433/4 589) respectively. The prevalence of blindness and moderate and severe visual impairment defined as presenting visual acuity was 2.68% (123/4 589) and 18.15% (833/4 589) respectively. The prevalence of blindness and moderate and severe visual impairment was higher in aged (trend χ(2) = 1 239.34, P < 0.01) , female (χ(2) = 37.88, P < 0.01) and illiterate (trend χ(2) = 235.11, P < 0.01) persons. Cataract was the first leading cause of blindness and visual impairment.
The prevalence of blindness and moderate and severe visual impairment is higher among older adults aged 50 years or above in Yangxi County. Cataract remains as the first leading cause of blindness and visual impairment.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 03/2014; 50(3):167-72. DOI:10.3760/cma.j.issn.0412-4081.2014.03.003
[Show abstract][Hide abstract] ABSTRACT: Tetramethylpyrazine (TMP) is one of the active ingredients extracted from the Chinese herb Chuanxiong, which has been used to treat cerebrovascular and cardiovascular diseases, pulmonary diseases and cancer. However, the molecular mechanisms underlying the actions of TMP have not been fully elucidated. In a previous study we showed that TMP-mediated glioma suppression and neural protection involves the inhibition of CXCR4 expression. The SDF-1/CXCR4 axis plays a fundamental role in many physiological and pathological processes. In this study, we further investigated whether the regulation of the SDF-1/CXCR4 pathway is also involved in the TMP-mediated inhibition of neovascularization or fibrosis and improvement of microcirculation.
Using a scratch-wound assay, we demonstrated that TMP significantly suppressed the migration and tubule formation of the human umbilical vein endothelial cell line ECV304 in vitro. The expression of CXCR4 in ECV304 cells is notably down-regulated after TMP treatment. In addition, TMP significantly suppresses corneal neovascularization in a rat model of corneal alkali burn injury. The expression of CXCR4 on days 1, 3 and 7 post-injury was determined through RT-PCR analysis. Consistent with our hypotheses, the expression of CXCR4 in the rat cornea is significantly increased with alkali burn and dramatically down-regulated with TMP treatment. Moreover, TMP treatment significantly attenuates bleomycin-induced rat pulmonary fibrosis, while immunofluorescence shows a notably decreased amount of CXCR4-positive cells in the TMP-treated group. Furthermore, TMP significantly down-regulates the expression of CXCR4 in platelets, lymphocytes and red blood cells. Whole-blood viscosity and platelet aggregation in rats are significantly decreased by TMP treatment.
These results show that TMP exerts potent effects in inhibiting neovascularization, fibrosis and thrombosis under pathological conditions; thus, the underlying mechanism of TMP might partially contribute to the down-regulation of CXCR4.
PLoS ONE 02/2014; 9(2):e88176. DOI:10.1371/journal.pone.0088176 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the safety and efficacy of intravitreal injection of (99)Tc-MDP, a decay product of (99m)Tc-MDP, on the development of laser-induced choroidal neovascularization (CNV) in rhesus monkeys.
Experimental CNV was induced by argon laser with a small high-energy laser spot. Monkeys were given 50 μL of (99)Tc-MDP at a concentration of 0.005 μg/mL (n = 6) or 0.01 μg/mL (n = 6) by intravitreal injection once a week immediately after laser injury for a period of 56 days. Control animals were treated with the same volume of PBS (n = 6) in the same way. Eyes were monitored by ophthalmic examination, color fundus photography, fluorescence fundus angiography (FFA), optical coherence tomography (OCT) and histology. Incidences of grade 4 CNV lesions as well as the leakage areas of grade 4 CNVs on the late-phase of fluorescein angiograms were measured in a standardized, randomized and masked fashion fortnightly. The maximum widths and heights of grade 4 CNVs were also calculated by histology at the end of the experiment. Toxicity of (99)Tc-MDP on the retina was evaluated by electroretinogram (ERG) and histologic analysis.
(99)Tc-MDP reduced the incidences of grade 4 CNVs by 33.33 % and 39.40 % in the 0.005 μg/mL and 0.01 μg/mL groups, respectively, compared with the PBS group on day 28 (P < 0.05; n = 6). The leakage areas of grade 4 CNVs were smaller in the 0.005 μg/mL (0.7136 ± 0.0283 mm(2), p <0.01; n = 6) and 0.01 μg/mL (0.4351 ± 0.0349 mm(2), p < 0.01; n = 6) groups than those in the PBS control group (0.9373 ± 0.0455 mm(2); n = 6) in a dose-dependent manner on day 28. OCT and histology also showed that the sizes of CNVs were smaller in the (99)Tc-MDP treated groups than those in the PBS group. Although intravitreal injection of (99)Tc-MDP led to mild inflammatory reaction in the anterior chamber, histology and ERG findings demonstrated that (99)Tc-MDP did not cause any change in histological structure or function of the retina (p>0.05).
Intravitreal injection of (99)Tc-MDP can inhibit the development of laser-induced CNV without toxic effect on retina, suggesting that (99)Tc-MDP has therapeutic potential for CNV related diseases.
Albrecht von Graæes Archiv für Ophthalmologie 01/2014; 252(7). DOI:10.1007/s00417-013-2559-1 · 1.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate and compare the structural differences of the ciliary body in eyes with and without malignant glaucoma.
Twenty-seven consecutive patients diagnosed with malignant glaucoma in 1 eye after trabeculectomy were recruited. They were all originally diagnosed with primary angle closure (PAC) or PAC glaucoma (PACG). Twenty-seven PAC/PACG eyes of 27 patients who had undergone uneventful trabeculectomy in the same period were also recruited. They were comparable with the fellow eyes of the malignant glaucoma patients in terms of surgical type, glaucoma type, and stage.
A-scan ultrasonography and ultrasound biomicroscopy measurements were performed on the eyes with malignant glaucoma, the fellow eyes of the patients with malignant glaucoma, and the matched eyes.
Ciliary body parameters included maximum ciliary body thickness (CBTmax), ciliary body thickness at the point of the scleral spur (CBT0) and 1000 μm from the scleral spur (CBT1000), anterior placement of the ciliary body (APCB), and the trabecular-ciliary process angle (TCA). Biometric measurements including axial length, central anterior chamber depth (ACD), pupil diameter (PD), anterior chamber width, and lens vault (LV) were also recorded.
Average CBTmax were 0.545±0.088 (mean ± standard deviation), 0.855±0.170, and 0.960±0.127 mm in eyes with malignant glaucoma, their fellow eyes, and the matched eyes, respectively. Average APCB were 0.860±0.176, 0.608±0.219, and 0.427±0.139 mm, respectively. Average TCA were 18.49±4.12, 41.79±17.27, and 48.53±10.38 degrees, respectively. The CBTmax, CBT0, CBT1000, and TCA were smaller, whereas APCB was larger in eyes with malignant glaucoma compared with their fellow eyes (P < 0.01). The fellow eyes had larger APCB and smaller CBTmax and CBT0 than the matched eyes (P < 0.05). The ACD, anterior chamber width, and PD were smaller, whereas LV was larger in eyes with malignant glaucoma compared with their fellow eyes (P < 0.05). No differences were found in the ACD, anterior chamber width, PD, or LV between the fellow eyes of malignant glaucoma and matched eyes (P > 0.1).
The ciliary bodies were thinner and more anteriorly rotated in eyes with malignant glaucoma as well as in their fellow eyes, which may be the predisposing factor for malignant glaucoma.
[Show abstract][Hide abstract] ABSTRACT: To compare anterior chamber paracentesis (ACP) with standard medical management of acute primary angle closure (APAC).
Patients with APAC and intraocular pressure (IOP) ≥50 mm Hg were enrolled.
Patients were randomized to receive ACP and medical treatment (group 1) or medical management alone (group 2).
There were 26 patients (mean age 69.3 ± 10.4 years, 31 eyes) in group 1 and 28 patients (mean age 67.0 ± 9.7 years, 30 eyes) in group 2. The IOP in group 1 was significantly lower at 15 minutes, 30 minutes, and 1 hour after treatment (p < 0.05). At 1, 2, and 24 hours after treatment, visual acuity was significantly better in group 1 than in group 2. At each time point after treatment, the grade of corneal edema was not different between the groups. Pain score at 1 and 2 hours after treatment was significantly lower in group 1 than in group 2; however, no difference was noted at 24 hours after treatment. The mean follow-up period in group 1 was 16.1 ± 1.3 months and in group 2 was 15.6 ± 1.4 months (p = 0.803). At last follow-up, IOP, pupil size, number of eyes with nonreactive pupils, and centre endothelial cell counts were not different; however, visual acuity was significantly better in group 1 (0.43 ± 0.06 logMAR vs 0.74 ± 0.10 logMAR, p = 0.007).
Immediate ACP is a safe and effective for rapidly lowering IOP, and is associated with better visual acuity than medical treatment alone.
Canadian Journal of Ophthalmology 12/2013; 48(6):553-8. DOI:10.1016/j.jcjo.2013.04.012 · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To gain insight into the potential mechanism of mitochondria dysfunction in pathogenesis, progression and therapeutic management of glaucoma.
The data used in this review were mainly published in English from 2000 to present obtained from PubMed. The search terms were "mitochondria", "glaucoma" and "trabecular meshwork" or "retinal ganglion cells".
Articles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed.
Mitochondrial dysfunction or injury was demonstrated in different eye tissue of glaucoma. A variety of potential injuries (light, toxic materials, oxidative injury, mechanical stress, aging, etc.) and the inherent DNA defects are deemed to cause mitochondrial structural and functional destruction in trabecular meshwork cells, retinal ganglion cells, etc. of glaucoma. In addition, various new experimental and therapeutic interventions were used to preserve mitochondrial function, which may be useful for protecting against optic nerve degeneration or reducing the death of retinal ganglion cells in glaucoma.
Mitochondria play an important role in the pathogenesis of glaucoma, various strategies targeting mitochondrial protection might provide a promising way to delay the onset of glaucoma or protect RGCs against glaucomatous damage.
Chinese medical journal 11/2013; 126(22):4358-65. DOI:10.3760/cma.j.issn.0366-6999.20131956 · 1.05 Impact Factor