[Show abstract][Hide abstract] ABSTRACT: To compare the efficacy and safety of the intraocular lens (IOL)-shell procedure versus conventional phacoemulsification for the surgical treatment of dense cataracts.
PLoS ONE 11/2014; 9(11):e112663. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Blood vessel degeneration is critically involved in nearly all types of degenerative diseases. Therefore strategies to enhance blood vessel protection and survival are highly needed. In this study, using different animal models and cultured cells, we show that PDGF-CC is a potent vascular protective and survival factor. PDGF-CC deficiency by genetic deletion exacerbated blood vessel regression/degeneration in various animal models. Importantly, treatment with PDGF-CC protein not only increased the survival of retinal blood vessels in a model of oxygen-induced blood vessel regression but also markedly rescued retinal and blood vessel degeneration in a disease model of retinitis pigmentosa. Mechanistically, we revealed that heme oxygenase-1 (HMOX1) activity is critically required for the vascular protective/survival effect of PDGF-CC, because blockade of HMOX1 completely abolished the protective effect of PDGF-CC in vitro and in vivo. We further found that both PDGF receptors, PDGFR-β and PDGFR-α, are required for the vasoprotective effect of PDGF-CC. Thus our data show that PDGF-CC plays a pivotal role in maintaining blood vessel survival and may be of therapeutic value in treating various types of degenerative diseases.
Proceedings of the National Academy of Sciences 09/2014; · 9.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the bacterial contamination risk in cataract surgery associated with mechanical compression of the lid margin immediately after sterilization of the ocular surface.
Journal of Cataract and Refractive Surgery 08/2014; 40(8):1377-81. · 2.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Congenital cataract (CC) is the primary cause of treatable childhood blindness. Population-based assessments of prevalence and surgery age of CC, which are critical for improving management strategies, have been unavailable in China until now. We conducted a hospital-based, cross-sectional study of the hospital charts of CC patients younger than 18 years old from January 2005 to December 2010 at Zhongshan Ophthalmic Center (ZOC) in Guangzhou, China. Residence, gender, age at surgery, hospitalization time, and the presence of other ocular abnormalities were extracted and statistically analyzed in different subgroups. The search identified 1314 patients diagnosed with CC from a total of 136154 hospitalizations, which accounted for 2.39% of all the cataract in-patients and 1.06% of the total in-patients over the six-year study period. Of the identified CC patients, 9.2% had ≥2 hospitalizations due to the necessity of additional surgeries, with a total ratio of boys to girls of 1.75∶1. Based on a subgroup analysis according to age, patients 2-6 years old constituted the highest proportion (29.22%) of all hospitalized CC patients, and those 13-18 years old constituted the lowest proportion (13.47%) of the total number. The average age at surgery was 27.62±23.36 months, but CC patients ≤6 years old (especially ≤6 months old) became increasingly prevalent throughout the 6-year study period. A total of 276 cases (20.93%) of CC were associated with one or more other ocular abnormalities, the highest incidence rates were observed for exotropia (6.24%), nystagmus (6.16%), and refractive error (3.65%). In conclusion, CC patients accounted for 2.39% of all cataract in-patients in a review of 6 years of hospitalization charts from ZOC. The age at the time of surgery decreased over the 6-year study period, which probably reflects the continuing improvement of public awareness of children's eye care in China.
PLoS ONE 07/2014; 9(7):e101781. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells is a major pathologic change in the development of proliferative vitreoretinopathy (PVR), which leads to severe visual impairment. ERK1/2 pathway has been reported to play a key role in the carcinogenesis, cancer metastasis, and multiple fibrotic diseases. We hypothesized that ERK1/2 signaling could cross-interact with transforming growth factor β2 (TGFβ2)/Smad and Notch signaling pathways in the regulation of EMT in RPE cells. Here, we demonstrated that ERK1/2 signaling was activated in TGFβ2-induced EMT in human RPE cells, while blockade of the canonical TGFβ2/Smad2/3 signaling with SB431542 could not inhibit TGFβ2-induced the activation of ERK1/2. Meanwhile, blockade of ERK1/2 signaling with a specific MEK/ERK1/2 inhibitor U0126 strongly prevented TGFβ2-induced the downregulation of P-cadherin, and the upregulation of α-SMA, collagen type IV, N-cadherin and fibronectin in RPE cells. In addition, we also identified that blockade of ERK1/2 signaling could inhibit not only the canonical TGFβ/Smad signaling, but also the Jagged/Notch pathway. Finally, we found that blockade of Notch pathway with a specific inhibitor DAPT could inhibit TGFβ2-induced the activation of ERK1/2 pathway conversely. Therefore, our study provides evidence that ERK1/2 signaling can cross-interact with the canonical TGFβ/Smad and the Jagged/Notch signaling pathways in RPE cells EMT. ERK1/2 inhibitor may have therapeutic value in the prevention and treatment of PVR and other fibrotic diseases.
PLoS ONE 05/2014; 9(5):e96365. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is the major pathological mechanism in anterior subcapsular cataract (ASC) and posterior capsule opacification (PCO), which are important causes of visual impairment. Extracellular signal-regulated kinase (ERK)1/2 pathway has been reported to play a major role in carcinogenesis, cancer metastasis and various fibrotic diseases. We hypothesized that ERK1/2 signaling can cross-interact with canonical transforming growth factor β (TGFβ)/Smad signaling and the Notch pathway, which subsequently contributes to LECs EMT. In this study, we demonstrated that ERK1/2 signaling was activated in TGFβ2‑induced EMT in human LECs, whereas the blockade of TGFβ2/Smad2/3 signaling with SB431542 did not inhibit the activation of ERK1/2 induced by TGFβ2. In addition, inactivation of ERK1/2 signaling with a specific MEK/ERK1/2 inhibitor, U0126, completely prevented the TGFβ2-induced upregulation of α-SMA, collagen type I, collagen type IV and fibronectin. We also demonstrated that inactivation of ERK1/2 signaling inhibited canonical TGFβ/Smad signaling, as well as the Jagged/Notch pathway. By contrast, blockade of the Notch pathway by DAPT inhibited the TGFβ2‑induced activation of ERK1/2 pathway in LECs. Thus, results of this study provide evidence for the complex interplay between ERK1/2, TGFβ/Smad, and Jagged/Notch signaling pathways in the regulation of EMT in LECs. Inhibition of the ERK1/2 pathway may therefore have therapeutic value in the prevention and treatment of ASC and PCO.
International Journal of Molecular Medicine 04/2014; · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells plays a key role in proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), both of which lead to severe loss of vision. Recently, microRNAs (miRNAs) have been found to be involved in the regulation of various physiological and pathological processes, such as embryogenesis, organ development, oncogenesis and angiogenesis. However, the expression profile and function of miRNAs in the EMT of RPE cells remain to be clarified. In this study, human miRNA expression profiles were identified using microarrays and 304 miRNAs were found to be differentially expressed in TGFβ2-induced EMT in human RPE cells. Of these differentially expressed miRNAs, 185 miRNAs were downregulated and 119 miRNAs were upregulated at least 2-fold in TGFβ2 treatment samples. Similar alterations of miRNA expression were validated for 35 representative miRNAs by quantitative polymerase chain reaction analysis. Therefore, these results suggested that differentially expressed miRNAs play potential roles in TGFβ2-induced EMT in RPE cells. This is an essential step in the identification of miRNAs associated with PVR and PDR progression, and in the identification of potential therapeutic targets for these diseases.
International Journal of Molecular Medicine 03/2014; · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The proliferation and epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells are the major pathological changes in development of proliferative vitreoretinopathy (PVR), which leads to severe visual impairment. Histone deacetylases (HDACs)-mediated epigenetic mechanisms play important roles in controlling various physiological and pathological events. However, whether HDACs are involved in the regulation of proliferation and EMT in PRE cells remains unidentified. In this study, we evaluated the expression profile of HDAC family (18 genes) and found that some of class I and class II HDACs were up-regulated in transforming growth factor-β2 (TGF-β2)/TGF-β1-stimulated RPE cells. Tricostatin A (TSA), a class I and II HDAC inhibitor, suppressed the proliferation of RPE cells by G1 phase cell cycle arrest through inhibition of cyclin/CDK/p-Rb and induction of p21 and p27. In the meantime, TSA strongly prevented TGF-β2-induced morphological changes and the up-regulation of α-SMA, collagen type I, collagen type IV, fibronectin, Snail and Slug. We also demonstrated that TSA affected not only the canonical Smad signalling pathway but also the non-canonical TGF-β/Akt, MAPK and ERK1/2 pathways. Finally, we found that the underlying mechanism of TSA affects EMT in RPE cells also through down-regulating the Jagged/Notch signalling pathway. Therefore, this study may provide a new insight into the pathogenesis of PVR, and suggests that epigenetic treatment with HDAC inhibitors may have therapeutic value in the prevention and treatment of PVR.
Journal of Cellular and Molecular Medicine 01/2014; · 3.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Congenital cataract is a major cause of visual impairment and childhood blindness. The solubility and stability of crystallin proteins play critical roles in maintaining the optical transparency of the lens during the life span. Previous studies have shown that approximately 8.3%∼25% of congenital cataracts are inherited, and mutations in crystallins are the most common. In this study, we attempted to identify the genetic defect in a four-generation family affected with congenital cataracts. The congenital cataract phenotype of this four-generation family was identified as membranous cataract by slit-lamp photography. Mutation screening of the candidate genes detected a heterozygous c.465G→C change in the exon6 of the βB2-crystallin gene (CRYBB2) in all family members affected with cataracts, resulting in the substitution of a highly conserved Tryptophan to Cystine (p.W151C). The mutation was confirmed by restriction fragment length polymorphism (RFLP) analysis and found that the transition res
PLoS ONE 11/2013; 8(11):e81290. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Monitoring intraocular pressure (IOP) is essential for pediatric cataract treatment but always difficult due to lack of cooperation in young children. We present the baseline characteristics and the first-year results of a long-term prospective cohort study, which are aimed to determine the relationship of the incidence of ocular hypertension (OH) in children after cataract surgery during the first-year period and the risk of developing late-onset glaucoma. Children were included with the following criteria: they were≤10 years old and scheduled to undergo cataract surgery with/without intraocular lens implantation; they were compliant with our follow-up protocol, which included monitoring IOP using a Tono-Pen under sedation or anesthesia. Incidence of OH, peak OH value, OH onset time and OH duration within a 12-month period following surgery were measured. In brief, 206 patients (379 eyes) were included and OH developed in 66 of 379 (17.4%) eyes. The mean follow-up period was 14.0±3.2 months (med
PLoS ONE 07/2013; 8(7):e69867. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown. Here, we show that the cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development of atherosclerotic lesions in mice. In two genetic mouse knockout models (apolipoprotein E(-/-) [ApoE(-/-)] and LDL receptor(-/-) [Ldlr(-/-)] mice), persistent cold exposure stimulated atherosclerotic plaque growth by increasing lipid deposition. Furthermore, marked increase of inflammatory cells and plaque-associated microvessels were detected in the cold-acclimated ApoE(-/-) and Ldlr(-/-) mice, leading to plaque instability. Deletion of uncoupling protein 1 (UCP1), a key mitochondrial protein involved in thermogenesis in brown adipose tissue (BAT), in the ApoE(-/-) strain completely protected mice from the cold-induced atherosclerotic lesions. Cold acclimation markedly reduced plasma levels of adiponectin, and systemic delivery of adiponectin protected ApoE(-/-) mice from plaque development. These findings provide mechanistic insights on low-temperature-associated cardiovascular risks.
[Show abstract][Hide abstract] ABSTRACT: It is well established that the tumor suppressor p53 plays major roles in regulating apoptosis and cell cycle progression. In addition, recent studies have demonstrated that p53 is actively involved in regulating cell differentiation in muscle, the circulatory system and various carcinoma tissues. We have recently shown that p53 also controls lens differentiation. Regarding the mechanism, we reveal that p53 directly regulates c-Maf and Prox1, two important transcription factors to control cell differentiation in the ocular lens. In the present study, we present further evidence to show that p53 can regulate lens differentiation by controlling expression of the differentiation genes coding for the lens crystallins. First, the aA and bA3/A1 gene promoters or introns all contain putative p53 binding sites. Second, gel mobility shifting assays revealed that the p53 protein in nuclear extracts from lens epithelial cells directly binds to the p53 binding sites found in these crystallin gene promoters or introns. Third, exogenous wild type p53 induces dose-dependent expression of the luciferase reporter gene driven by different crystallin gene promoters and the exogenous dominant negative mutant p53 causes dose-dependent inhibition of the same crystallin genes. Fourth, ChIP assays revealed that p53 binds to crystallin gene promoters in vivo. Finally, in the p53 knockout mouse lenses, expression levels of various crystallins were found down-regulated in comparison with those from the wild type mouse lenses. Together, our results reveal that p53 directly regulates expression of different sets of genes to control lens differentiation.
Current Molecular Medicine 06/2013; · 3.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Congenital cataract is the main cause of blindness in children, with significantly varying treatment effects. The development of axial length is an important factor that affects the prognosis of these children. However, when compared with the eyes of normal children, the mechanism of growth of the axial length is so complicated that the reported findings differ significantly in terms of the measuring apparatus, assessment methods, and statistical outcome, making the rule of axial length development still unclear. In this paper, we first review the process of axial length development in normal healthy children and compare different hypotheses about certain factors that could affect the development of axial length. The results of some current research about the characteristics of axial length development in congenital cataract children are then reviewed. Lastly, the advantages and disadvantages of current axial length measurements methods are compared and analyzed. The purpose of this review is to improve our understanding of the complexity and importance of axial length development and to suggest better use of axial length monitoring measurements in congenital cataract children for pediatric ophthalmologists, with the hope of offering assistance that will enhance long-term therapeutic effects for these children.
[Show abstract][Hide abstract] ABSTRACT: The importance of neurovascular crosstalk in development, normal physiology, and pathologies is increasingly being recognized. Although vascular endothelial growth factor (VEGF), a prototypic regulator of neurovascular interaction, has been studied intensively, defining other important regulators in this process is warranted. Recent studies have shown that platelet-derived growth factor C (PDGF-C) is both angiogenic and a neuronal survival factor, and it appears to be an important component of neurovascular crosstalk. Importantly, the expression pattern and functional properties of PDGF-C and its receptors differ from those of VEGF, and thus the PDGF-C-mediated neurovascular interaction may represent a new paradigm of neurovascular crosstalk.
Trends in Molecular Medicine 05/2013; · 10.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pediatric ophthalmologists increasingly recognize that the ideal site for intraocular lens (IOL) implantation is in the bag for aphakic eyes, but it is always very difficult via conventional technique. We conducted a prospective case series study to investigate the success rate and clinical outcomes of capsular bag reestablishment and in-the-bag IOL implantation via secondary capsulorhexis with radiofrequency diathermy (RFD) in pediatric aphakic eyes, in which twenty-two consecutive aphakic pediatric patients (43 aphakic eyes) enrolled in the Childhood Cataract Program of the Chinese Ministry of Health were included. The included children underwent either our novel technique for secondary IOL implantation (with RFD) or the conventional technique (with a bent needle or forceps), depending on the type of preoperative proliferative capsular bag present. In total, secondary capsulorhexis with RFD was successfully applied in 32 eyes (32/43, 74.4%, age 5.6±2.3 years), of which capsular bag reestablishment and in-the-bag IOL implantation were both achieved in 30 eyes (30/43, 70.0%), but in the remaining 2 eyes (2/32, 6.2%) the IOLs were implanted in the sulcus with a capsular bag that was too small. Secondary capsulorhexis with conventional technique was applied in the other 11 eyes (11/43, 25.6%, age 6.9±2.3 years), of which capsular bag reestablishment and in-the-bag IOL implantation were both achieved only in 3 eyes(3/43, 7.0%), and the IOLs were implanted in the sulcus in the remaining 8 eyes. A doughnut-like proliferative capsular bag with an extensive Soemmering ring (32/43, 74.4%) was the main success factor for secondary capsulorhexis with RFD, and a sufficient capsular bag size (33/43, 76.7%) was an additional factor in successful in-the-bag IOL implantation. In conclusion, RFD secondary capsulorhexis technique has 70% success rate in the capsular bag reestablishment and in-the-bag IOL implantation in pediatric aphakic eyes, particularly effective in cases with a doughnut-like, extensively proliferative Soemmering ring.
PLoS ONE 04/2013; 8(4):e62381. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aberrant spreading of lens epithelial cells along the posterior capsule is the basis for development of glucocorticoid (GC)-induced cataract; the resulting foci of nucleated cells at the posterior pole causing disruptions to normal lens cellular architecture. In this study, rat lens epithelial explants were used to assess the effects of dexamethasone (DEX), a widely used synthetic GC, on FGF2-induced lens cell proliferation and elongation as well as the ability of lens cells to spread and cover the posterior capsule. In the presence of FGF2, DEX significantly promoted lens cell proliferation after 48 hours. Cell coverage of the posterior capsule was also enhanced during 5 days culture. In contrast, cell elongation was retarded by the inclusion of DEX. In the absence of FGF2, DEX had no marked effects on any of these cellular processes. Thus, in the presence of FGF2, DEX promoted cell proliferation and posterior capsule coverage but inhibited cell elongation. These results provide insights into the molecular mechanism underlying GC-induced cataract in humans.
Experimental Eye Research 03/2013; · 3.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: We sought to assess the perceived difficulty of steps of manual small incision cataract surgery (MSICS) among trainees in rural China. DESIGN: Cohort study. PARTICIPANTS: Fifty-two trainees at the end of a MSICS training program, METHODS: Participants rated the difficulty of 14 surgical steps using a 5-point scale, 1 (very easy) to 5 (very difficult). Demographic and professional information was recorded for trainees. MAIN OUTCOME MEASURE: Mean ratings for surgical steps. RESULTS: Questionnaires were completed by 49 trainees (94.2%, median age 38 years, 8 [16.3%] women.) Twenty-six (53.1%) had performed < 50 independent cataract surgeries prior to training. Trainees rated cortical aspiration (mean score ± standard deviation [SD] = 3.10 ± 1.14) the most difficult step, followed by wound construction ( 2.76±1.08), nuclear prolapse into the anterior chamber (2.74±1.23) and lens delivery (2.51±1.08). Draping the surgical field (1.06±0.242), anesthetic block administration (1.14±0.354) and thermal coagulation (1.18±0.441) were rated easiest. In regression models, the difficulty score for cortical aspiration was significantly inversely associated with performing > 50 independent MSICS surgeries during training (P = 0.01), but not significantly associated with age, gender, years of experience in an eye department or total number of cataract surgeries performed prior to training. CONCLUSIONS: Cortical aspiration, wound construction and nuclear prolapse pose the greatest challenge for trainees learning MSICS, and should receive emphasis during training. Numbers of cases performed is the strongest predictor of perceived difficulty of key steps.
Clinical and Experimental Ophthalmology 01/2013; · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate whether lymphatic microvessel density (LMVD) could be used as a predictive marker for the recurrence time of pterygia.
This was a prospective case series study. Ninety-six patients with unilateral eye primary nasal pterygia were included. The patients were clinically evaluated to grade the severity of their pterygia (32 were Grade 1, 29 were Grade 2, and 35 were Grade 3) before they underwent bare sclera resection with the use of mitomycin C. Excised tissues from the 96 patients and the ten normal nasal conjunctiva obtained from age-matched donor eyeballs (controls) were immunostained with LYVE-1 and CD31 monoclonal antibodies to evaluate LMVD and blood microvessel density (BMVD). The patients were followed up for three years or until pterygium recurrence was identified, which was defined as fibrovascular regrowth past the limbus in a previously compromised area. The recurrence time (RT) for a pterygium was calculated, and its relationship with LMVD and/or BMVD was statistically analyzed.
In total, there were 24 cases of pterygium recurrence. The recurrence rate of Grade 1 was 28.1% (9/32), Grade 2 was 24.1% (7/29), and Grade 3 was 22.9% (8/35), as classified in the primary pterygium (p>0.05); the overall recurrence rate was 25% (24/96) for all patients during the three-year follow-up. In the tissue analysis, there were a small number of CD31 (+), LYVE-1(-) BMVD and only a few CD31 (weak), LYVE-1(+) LMVD in the ten normal nasal conjunctiva tissues. BMVD and LMVD increased significantly in the pterygium tissue compared to the control tissue and were significantly correlated with the width and area of pterygium in Grades 1-3 (all p values <0.05). RT was not correlated with BMVD or pterygium grade, but LMVD was significantly and negatively correlated with RT within each group and in the total patient cohort. Furthermore, we determined that an LMVD greater than 20 in the surgical specimens predicted pterygium recurrence.
The LMVD of surgical specimens is an independent risk factor and a valuable predictive factor for the recurrence time of pterygia.