Yizhi Liu

Sun Yat-Sen University, Shengcheng, Guangdong, China

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Publications (104)571.9 Total impact

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    ABSTRACT: Soft-lens cataract surgeries are becoming increasingly common for cataract surgeons and chopping the soft nucleus using conventional techniques is problematic. We introduced a femtosecond laser combined with a non-chopping rotation phacoemulsification technique for soft-nucleus cataract surgery and evaluated the safety and efficacy of using this technique. Sixty-six patients with soft-nucleus cataracts ranging from grade 1∼3 were divided into 3 groups based on nuclear staging. Those groups were further divided into three subgroups: femtosecond laser pretreatment combined with a non-chopping rotation phacoemulsification technique (subgroup 1), conventional manual cataract surgery with a non-chopping rotation technique (subgroup 2) and conventional manual cataract surgery with a quick-chop technique (subgroup 3).Patients were followed up at 1, 7, and 30 days after surgery. There was an 84.6% and a 63.34% reduction in ultrasound time and cumulative dissipated energy, respectively, between the subgroup 1 and the subgroup 3; and this was associated with a 36.1% and 29.7% reduction in endothelial cell loss and aqueous flare. There were no adverse events at the follow-up times. With its reduced ultrasound energy, endothelial cell loss and aqueous flare, the femtosecond laser pretreatment combined with a non-chopping rotation technique was more efficient than conventional manual cataract surgery for soft-nucleus cataracts.
    Preview · Article · Jan 2016 · Scientific Reports
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    ABSTRACT: A review of 6 years of hospitalization charts from Zhongshan Ophthalmic Center (ZOC) revealed that congenital cataracts (CC) accounted for 2.39% of all cataract in-patient cases and that the age at surgery was decreasing before the establishment of the Childhood Cataract Program of the Chinese Ministry of Health (CCPMOH) in December 2010. We aimed to investigate data from the 4 years (January 2011 to December 2014) following the establishment of the CCPMOH, compared, and combined with data from the previous study period (January 2005 to December 2010) to generate a 10-year overview of the hospital-based prevalence and treatment of CC. In the 4-year period after CCPMOH establishment, the prevalence of CC was 2.01% in all hospitalizations, and was 2.78% in all cataract in-patients. Most of the eligible CC in-patients (71%) lived in south China. The ratio of boys to girls was 1.42:1. Nearly 2/3 of the patients underwent cataract extraction with primary intraocular lens (IOL) implantation at a mean age of 78.40±51.45 months, and cataract extraction surgeries without IOL implantation were performed in the remaining 1/3 of patients at a mean age of 10.03±15.92 months. After CCPMOH establishment, an increased incidence of CC was revealed, and the CC in-patients were younger than the patients in the previous period. The 10-year overview (2421 CC in-patients from 206630 hospitalizations) revealed upward trends in both the number and the prevalence of CC and a further reduction in age at surgery. In conclusion, the data from 4-year period after CCPMOH establishment and the 10-year overview showed upward trends in the hospital-based prevalence of CC cases and a further reduction in age at surgery, likely reflecting the effects of the CCPMOH establishment and providing useful information for further CC studies and a valuable foundation for the prevention and treatment of this cause of childhood blindness.
    Full-text · Article · Nov 2015 · PLoS ONE
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    ABSTRACT: Capsular outcomes of anterior/posterior capsulorhexis opening (ACO/PCO) are essential for performing a secondary in-the-bag intraocular lens implantation. To compare the capsular outcomes with different primary capsulorhexis sizes, Thirty-eight eligible patients (45 eyes) were randomly assigned to three groups by anterior capsulorhexis diameter (Group A: 3.0-3.9, Group B: 4.0-5.0, and Group C: 5.1-6.0 mm). The areas of ACO/PCO and posterior capsule opening opacity (PCOO) as primary outcomes, while, the incidence of visual axis opacity (VAO) as secondary outcome were measured at follow-up visits. Among the thirty eyes included in the final analysis, the mean area of the ACO decreased significantly, whereas the PCO enlarged with time. Group A had the highest anterior capsule constriction and percentage reduction, which increased with time. There were significant differences in the percentage reductions at 6 months and 1 year compared to 1 month in Group A and B. Group C had the highest posterior capsule enlargement. The percentage of PCOO to PCO area and the incidence of VAO was highest in Group A and lowest in Group C. Thus, Capsulorhexis diameter of 4.0-5.0 mm may yield better capsular outcomes, considering moderate contraction of ACO, moderate enlargement of PCO, and lower percentage of PCOO and VAO.
    Full-text · Article · Nov 2015 · Scientific Reports

  • No preview · Article · Oct 2015 · Nature
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    ABSTRACT: Physiological functions of vascular endothelial growth factor (VEGF)-B remain an enigma, and deletion of the Vegfb gene in mice lacks an overt phenotype. Here we show that knockdown of Vegfba, but not Vegfbb, in zebrafish embryos by specific morpholinos produced a lethal phenotype owing to vascular and neuronal defects in the brain. Vegfba morpholinos also markedly prevented development of hyaloid vasculatures in the retina, but had little effects on peripheral vascular development. Consistent with phenotypic defects, Vegfba, but not Vegfaa, mRNA was primarily expressed in the brain of developing zebrafish embryos. Interestingly, in situ detection of Neuropilin1 (Nrp1) mRNA showed an overlapping expression pattern with Vegfba, and knockdown of Nrp1 produced a nearly identically lethal phenotype as Vegfba knockdown. Furthermore, zebrafish VEGF-Ba protein directly bound to NRP1. Importantly, gain-of-function by exogenous delivery of mRNAs coding for NRP1-binding ligands VEGF-B or VEGF-A to the zebrafish embryos rescued the lethal phenotype by normalizing vascular development. Similarly, exposure of zebrafish embryos to hypoxia also rescued the Vegfba morpholino-induced vascular defects in the brain by increasing VEGF-A expression. Independent evidence of VEGF-A gain-of-function was provided by using a functionally defective Vhl-mutant zebrafish strain, which again rescued the Vegfba morpholino-induced vascular defects. These findings show that VEGF-B is spatiotemporally required for vascular development in zebrafish embryos and that NRP1, but not VEGFR1, mediates the essential signaling.
    No preview · Article · Oct 2015 · Proceedings of the National Academy of Sciences
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    ABSTRACT: Translational control is crucial in the regulation of gene expression and deregulation of translation is associated with a wide range of cancers and human diseases. Ribosome profiling is a technique that provides genome wide information of mRNA in translation based on deep sequencing of ribosome protected mRNA fragments (RPF). RPFdb is a comprehensive resource for hosting, analyzing and visualizing RPF data, available at www.rpfdb.org or http://sysbio.sysu.edu.cn/rpfdb/index.html. The current version of database contains 777 samples from 82 studies in 8 species, processed and reanalyzed by a unified pipeline. There are two ways to query the database: by keywords of studies or by genes. The outputs are presented in three levels. (i) Study level: including meta information of studies and reprocessed data for gene expression of translated mRNAs; (ii) Sample level: including global perspective of translated mRNA and a list of the most translated mRNA of each sample from a study; (iii) Gene level: including normalized sequence counts of translated mRNA on different genomic location of a gene from multiple samples and studies. To explore rich information provided by RPF, RPFdb also provides a genome browser to query and visualize context-specific translated mRNA. Overall our database provides a simple way to search, analyze, compare, visualize and download RPF data sets.
    Full-text · Article · Oct 2015 · Nucleic Acids Research
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    ABSTRACT: Glaucoma, a blinding neurodegenerative disease, whose risk factors include elevated intraocular pressure (IOP), age, and genetics, is characterized by accelerated and progressive retinal ganglion cell (RGC) death. Despite decades of research, the mechanism of RGC death in glaucoma is still unknown. Here, we demonstrate that the genetic effect of the SIX6 risk variant (rs33912345, His141Asn) is enhanced by another major POAG risk gene, p16INK4a (cyclin-dependent kinase inhibitor 2A, isoform INK4a). We further show that the upregulation of homozygous SIX6 risk alleles (CC) leads to an increase in p16INK4a expression, with subsequent cellular senescence, as evidenced in a mouse model of elevated IOP and in human POAG eyes. Our data indicate that SIX6 and/or IOP promotes POAG by directly increasing p16INK4a expression, leading to RGC senescence in adult human retinas. Our study provides important insights linking genetic susceptibility to the underlying mechanism of RGC death and provides a unified theory of glaucoma pathogenesis.
    Full-text · Article · Sep 2015 · Molecular cell
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    ABSTRACT: Purpose: To investigate the expression of αA- and αB-crystallin and the unfolded protein response in the lens epithelium of patients with high myopia-related cataracts. Methods and materials: The central portion of the human anterior lens capsule together with the adhering epithelial cells, approximately 5 mm in diameter, were harvested and processed within two hours after cataract surgery from high myopia-related (spherical equivalent ≥-10.00 diopters) and age-related cataract patients or from high myopia but non-cataractous patients (tissue were collected from ocular trauma patients with high myopia and lens trauma). Anterior lens samples from fresh cadaver normal human eyes were used as normal control (collected within 6 hours from death). Real-time PCR was performed to detect the mRNA levels of α-crystallins as well as unfolded protein response (UPR)-related GRP78, spliced-XBP1, ATF4 and ATF6. Western blot analysis was used to determine the protein level of α-crystallin, GRP78, p-IRE1α, p-eIF2α and ATF6. Results: In the lens epithelium of the high myopia-related cataract group and the age related cataract group, the mRNA and soluble protein expression of αA- and αB-crystallin were both decreased; additionally, the protein levels of ATF6, p-eIF2α and p-IRE1α and the gene expression levels of spliced XBP1, GRP78, ATF6 and ATF4 were greatly increased relative to the normal control. Conclusion: These results suggest the significant loss of soluble α-crystallin and the activation of the UPR in the lens epithelium of patients with high myopia-related cataract, which may be associated with the cataractogenesis of high myopia-related cataract.
    Preview · Article · Sep 2015 · PLoS ONE
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    Haotian Lin · Erping Long · Weirong Chen · Yizhi Liu

    Full-text · Article · Sep 2015 · Science
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    ABSTRACT: To describe cytokines, chemokines and growth factors profiles in patients undergoing cataract surgery with femtosecond laser pretreatment and investigate their relationships with the postoperative in vivo inflammation index. Aqueous humor was collected from 22 eyes after femtosecond laser pretreatment and from 22 eyes at the beginning of routine cataract surgery. The levels of 45 inflammation-related mediators were measured using multiplex fluorescent bead-based immunoassays. Laser flare photometry was measured preoperatively and at 1 day, 7 days and 30 days postoperatively. Compared with the control group, the femtosecond laser treatment group showed significantly higher aqueous humor levels of fibroblast growth factor (FGF-2), tumor necrosis factor (TNF)-α, leukemia inhibitor factor (LIF), interleukin (IL)-1ra and IL-18, and significantly lower aqueous humor levels of IL-9, platelet-derived growth factor (PDGF)-BB, eotaxin and TNF-β. Postoperative aqueous flare was significantly greater in the manual cataract surgery group at 1 day (p<0.001), 7days (p<0.001) and 30 days (p = 0.002).No correlation was found between the analyzed mediators and the aqueous flare values. The expression profiles of cytokines, chemokines and growth factors and the correlations of these profiles with the in vivo inflammatory indexes for patients undergoing cataract surgery with femtosecond laser pretreatment were identified. Our data indicate a disturbance of postoperative inflammation response after femtosecond laser treatment.
    Full-text · Article · Sep 2015 · PLoS ONE
  • Yizhi Liu · Frances Wu · Lin Lu · Danni Lin · Kang Zhang
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    ABSTRACT: Direct ophthalmoscopy is an important technique for examination of the retina that can be mastered with practice. It can be performed in minutes during the general medical examination and poses virtually no risks to the patient. Ophthalmoscopy allows the general practitioner to evaluate the retina for pathologic changes, particularly in patients with common systemic diseases such as diabetes, hypertension, or atherosclerosis. Ophthalmoscopy can also help to identify ophthalmic emergencies that require immediate attention.
    No preview · Article · Aug 2015 · New England Journal of Medicine
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    ABSTRACT: To study safety of children's glasses in rural China, where fear that glasses harm vision is an important barrier for families and policy-makers. Exploratory analysis from a cluster-randomized, investigator-masked, controlled trial. Among primary schools (n=252) in western China, children were randomized by school to one of three interventions: free glasses provided in class, vouchers for free glasses at a local facility or glasses prescriptions only (Control group). The main outcome of this analysis is uncorrected visual acuity after 8 months, adjusted for baseline acuity. Among 19,934 children randomly selected for screening, 5852 myopic (spherical equivalent refractive error <= -0.5 D) eyes of 3001 children (14.7%, mean age 10.5 years) had VA <= 6/12 without glasses correctable to > 6/12 with glasses, and were eligible. Among these, 1903 (32.5%), 1798 (30.7%), and 2151 (36.8%) were randomized to Control, Voucher and Free Glasses respectively. Intention-to-treat analyses were performed on all 1831 (96.2%), 1699 (94.5%), and 2007 (93.3%) eyes of children with follow-up in Control, Voucher and Free Glasses groups. Final visual acuity for eyes of children in the treatment groups (Free Glasses and Voucher) was significantly better than for Control children, adjusting only for baseline visual acuity (difference of 0.023 logMAR units [0.23 vision chart lines, 95% CI: 0.03, 0.43]) or for other baseline factors as well (0.025 logMAR units [0.25 lines, 95% CI 0.04, 0.45]). We found no evidence that spectacles promote decline in uncorrected vision with aging among children. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Aug 2015 · American Journal of Ophthalmology
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    ABSTRACT: The aim of this study was to evaluate the efficacy and safety of femtosecond laser-assisted cataract surgery (FLACS) versus conventional phacoemulsification cataract surgery (CPCS) in the treatment of cataract. Randomized controlled trials (RCTs) were searched in PubMed, Embase and the Cochrane Central Register of Controlled Trials. Nine qualified studies with a total of 989 eyes were included. Compared with CPCS, FLACS significantly reduced mean phaco energy and effective phacoemulsification time (EPT) required in the surgery. Central corneal thickness (CCT) was significantly lower in FLACS at 1 day of follow-up, but CCT and corneal endothelial cells count was comparable at 1 week of follow-up or longer. FLACS achieved a better visual outcome at postoperative 1 week and 6 months, but the difference was not significant at postoperative 1-3 months. Regard to surgical complications, the incidences of intraoperative anterior capsule tear, postoperative macular edema and elevated intraocular pressure were similar. In conclusion, femtosecond laser pretreatment can reduce phaco energy and EPT, which may reduce the heat damage to ocular tissues by ultrasound. This novel technique might be beneficial for patients with dense cataract and/or low preoperative endothelial cell values. Well-designed RCTs with longer follow-up are still necessary to provide more reliable evidence.
    Preview · Article · Aug 2015 · Scientific Reports
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    ABSTRACT: The human lens is comprised largely of crystallin proteins assembled into a highly ordered, interactive macro-structure essential for lens transparency and refractive index. Any disruption of intra- or inter-protein interactions will alter this delicate structure, exposing hydrophobic surfaces, with consequent protein aggregation and cataract formation. Cataracts are the most common cause of blindness worldwide, affecting tens of millions of people, and currently the only treatment is surgical removal of cataractous lenses. The precise mechanisms by which lens proteins both prevent aggregation and maintain lens transparency are largely unknown. Lanosterol is an amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. Here we identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Both of these mutations affect highly conserved amino acid residues and impair key catalytic functions of LSS. Engineered expression of wild-type, but not mutant, LSS prevents intracellular protein aggregation of various cataract-causing mutant crystallins. Treatment by lanosterol, but not cholesterol, significantly decreased preformed protein aggregates both in vitro and in cell-transfection experiments. We further show that lanosterol treatment could reduce cataract severity and increase transparency in dissected rabbit cataractous lenses in vitro and cataract severity in vivo in dogs. Our study identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment.
    Full-text · Article · Jul 2015 · Nature
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    ABSTRACT: Retinoblastoma is a highly invasive malignant tumor that often invades the brain and metastasizes to distal organs through the blood stream. Invasiveness and metastasis of retinoblastoma can occur at the early stage of tumor development. However, an optimal preclinical model to study retinoblastoma invasiveness and metastasis in relation to drug treatment has not been developed. Here, we developed an orthotopic zebrafish model in which retinoblastoma invasion and metastasis can be monitored at a single cell level. We took the advantages of immune privilege and transparent nature of developing zebrafish embryos. Intravitreal implantation of color-coded retinoblastoma cells allowed us to kinetically monitor tumor cell invasion and metastasis. Further, interactions between retinoblastoma cells and surrounding microvasculatures were studied using a transgenic zebrafish that exhibited green fluorescent signals in blood vessels. We discovered that tumor cells invaded neighboring tissues and blood stream when primary tumors were at the microscopic sizes. These findings demonstrate that retinoblastoma metastasis occurs at the early stage and antiangiogenic drugs such as Vegf morpholino and sunitinib could potentially interfere with tumor invasiveness and metastasis. Thus, this orthotopic retinoblastoma model offers a new and unique opportunity to study the early events of tumor invasion, metastasis and drug responses.
    Full-text · Article · Jul 2015 · Scientific Reports
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    ABSTRACT: Purpose: To investigate the activation of three unfolded protein response (UPR) pathways in the lenses of age-related, high myopia-related and congenital cataracts. Methods and materials: Lens specimens were collected from patients during small incision cataract surgery. Lenses from young cadaver eyes were collected as normal controls. Real-time PCR and Western blotting were performed to detect the expression of GRP78, p-eIF2α, spliced XBP1, ATF6, ATF4 and p-IRE1α in the lenses of normal human subjects and patients with age-related, myopia-related or congenital cataracts. Results: In the lenses of the age-related and high myopia-related cataract groups, the protein levels of ATF6, p-eIF2α and p-IRE1α and the gene expression levels of spliced XBP1, GRP78, ATF6 and ATF4 were greatly increased. Additionally, in the congenital cataract group, the protein levels of p-eIF2α and p-IRE1α and the gene expression levels of spliced XBP1, GRP78 and ATF4 were greatly increased. However, the protein and gene expression levels of ATF6 were not up-regulated in the congenital cataract group compared with the normal control group. Conclusions: The UPR is activated via different pathways in the lenses of age-related, high myopia-related and congenital cataracts. UPR activation via distinct pathways might play important roles in cataractogenesis mechanisms in different types of cataracts.
    Preview · Article · Jun 2015 · PLoS ONE
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    ABSTRACT: PAX6 is a master regulatory gene involved in neuronal cell fate specification. It also plays a critical role in early eye field and subsequent limbal stem cell determination during eye development. Defects of PAX6 cause aniridia and limbal stem cell deficiency in humans, and the Small eye (Sey) phenotype in mice. However, how PAX6 specifies limbal stem cell (LSC) and corneal fates during eye development is not well understood. Here we show that PAX6 is expressed in the primitive eye cup and later in corneal tissue progenitors in early embryonic development. In contrast, P63 expression commences after that of PAX6 in ocular adnexal and skin tissue progenitors, and later on in LSCs. By using an in vitro feeder-free culture system, we show that PAX6 knockdown in LSCs leads to an upregulation of skin epidermal specific keratins Concomitant with differentiation to a skin fate. Using gene expression analysis, we identified involvement of Notch, WNT and TGFb signaling pathways in LSC fate determination. Thus, loss of PAX6 converts LSCs to epidermal stem cells, as demonstrated by a switch in keratin gene expression profile and by the appearance congenital dermoid tissue. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    No preview · Article · Jun 2015 · Journal of Biological Chemistry
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    Full-text · Article · Jun 2015 · BMJ (online)
  • Xiaoyun Chen · Wei Xiao · Yizhi Liu

    No preview · Conference Paper · Jun 2015
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    ABSTRACT: The purpose of the current study was to investigate the 11 bestrophin-1 (BEST1) exons in patients with best vitelliform macular dystrophy (BVMD), and to characterize the associated clinical features. Complete ophthalmic examinations were conducted on two families, and two family members were diagnosed with BVMD. Genomic DNA was extracted from the leukocytes of peripheral blood collected from the patients and their family members, in addition to 100 unrelated control subjects recruited from the same population. The polymerase chain reaction was used to amplify a total of 11 exons of the BEST1 gene, which were directly sequenced. Ophthalmic examinations, including best‑corrected visual acuity, slit‑lamp examination, fundus examination, fundus photography and fluorescein angiography imaging, as well as anterior segment analysis with Pentacam and optical coherence tomography, were conducted. The patients exhibited yellowish lesions in the macular area. A heterozygous mutation c.910_912delGAT (p.304del Asp) in exon 7 was identified in Case 1. A heterozygous BEST1 missense mutation c.685T>G (p.Trp229Gly) in exon 5 was identified in Case 2, but not in any of the unaffected family members or normal controls. Although BEST1 gene mutations and polymorphisms have previously been reported in various ethnic groups, the current study identified, for the first time to the best of our knowledge, two novel BEST1 gene mutations in patients with BVMD.
    Preview · Article · Apr 2015 · Molecular Medicine Reports

Publication Stats

1k Citations
571.90 Total Impact Points

Institutions

  • 2002-2015
    • Sun Yat-Sen University
      • State Key Laboratory of Oncology
      Shengcheng, Guangdong, China
  • 2012
    • Jinan University (Guangzhou, China)
      Shengcheng, Guangdong, China