Splicing factor polymorphisms, the control of VEGF isoforms and association with angiogenic eye disease.


PURPOSE:Alternative splicing of the last exon (exon 8) of vascular endothelial growth factor (VEGF) pre-mRNA is a key element in the balance of pro- and anti-angiogenic VEGF isoforms in exudative age-related macular degeneration (exAMD) and proliferative diabetic retinopathy (PDR). Three splicing factors, SRp40, ASF/SF2, and SRp55 are predicted to control alternative splicing by binding to exonic splice enhancers (ESE) in VEGF exon 8. This pilot study examines whether there is an association between angiogenic eye disease and splicing factor polymorphisms, and whether there are sequence variations in the alternative splice sites of the VEGF gene. MATERIALS AND METHODS:A case:control pilot study comparing 163 individuals with angiogenic eye disease (94 exAMD and 69 PDR patients) with 95 age-matched controls. Splicing factor polymorphisms were genotyped by Restriction Fragment Length Polymorphism (RFLP) and sequencing, and the VEGF alternatively spliced region was assessed by denaturing High Performance Liquid Chromatography (dHPLC) using a transgenomic WAVE heteroduplex analyzer. RESULTS:No variations were observed in the alternatively spliced region of VEGF exon 8. ASF/SF2 polymorphisms showed no association with exAMD or PDR. For PDR, we observed a trend in SRp40 (rs6573908) where the 5136CC genotype was more frequent in controls (p = 0.0517) and a significant association of the SRp55 (rs2235611), where the 2994C allele was more common in the PDR group (p = 0.03). This remained strong, but not significant, after logistic regression for age, sex, disease type, and duration (p = 0.06). CONCLUSIONS:The lack of variation in the VEGF alternatively spliced region suggests the importance of sequence conservation in this area in maintaining the balance of pro- and anti-angiogenic VEGF isoforms. The link between PDR and the SRp55 2994 polymorphism suggests a disease-specific association between factors controlling VEGF splicing and ocular angiogenesis.


Curr Eye Res


Current eye research


Carter JG,Cherry J,Williams K,Turner S,Bates DO,Churchill AJ




Has Abstract


2011-04-01 00:00:00












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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Kawashima H,Gregerson DS

    更新日期:1994-08-01 00:00:00

  • Calcium Dobesilate Prevents Neurodegeneration and Vascular Leakage in Experimental Diabetes.

    abstract:PURPOSE:The mechanisms involved in the reported beneficial effects of Calcium dobesilate monohydrate (CaD) for the treatment of diabetic retinopathy (DR) remain to be elucidated. The main aim of the present study is to examine whether CaD prevents early events in the pathogenesis of DR such as neurodegeneration and vas...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Solà-Adell C,Bogdanov P,Hernández C,Sampedro J,Valeri M,Garcia-Ramirez M,Pasquali C,Simó R

    更新日期:2017-09-01 00:00:00

  • Ocular manifestation of simian immunodeficiency syndrome (SAIDS).

    abstract::The management of opportunistic infections is a significant problem in acquired immunodeficiency syndrome (AIDS) and the development of more effective chemotherapeutic agents is needed. We present the ocular manifestations of an AIDS-like disease in rhesus monkeys experimentally infected with simian immunodeficiency v...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Conway MD,Didier P,Fairburn B,Soike KF,Martin L,Murphey-Corb M,Meiners N,Insler MS

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  • Serum-free culture of porcine and rabbit corneal epithelial cells.

    abstract::To better define the growth requirements for corneal epithelial cells, methods for serum-free culture were established. Sheets of corneal epithelium from eyes of swine and rabbits were obtained by dispase treatment of corneal buttons, and single cells and small clumps were obtained by further dissociation with trypsin...

    journal_title:Current eye research

    pub_type: 杂志文章


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  • Relationship between retinal fractal dimensions and retinal circulation in patients with type 2 diabetes mellitus.

    abstract:PURPOSE:To investigate the relationship between retinal fractal dimensions (Dfs) and retinal circulation, which is impaired in early-stage diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM). METHODS:Using a laser Doppler velocimetry system, we measured the retinal vessel diameter (D) and blood ve...

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    更新日期:2013-11-01 00:00:00

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    journal_title:Current eye research

    pub_type: 杂志文章


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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Johnson DH,Richardson TM,Epstein DL

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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: O'Day DM,Head WS,Robinson RD,Williams TE,Gedde S

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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Kanamoto T,Okumichi H,Rimayanti U,Kiuchi Y

    更新日期:2011-01-01 00:00:00

  • Mini-Review: Impaired Axonal Transport and Glaucoma.

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    journal_title:Current eye research

    pub_type: 杂志文章,评审


    authors: Fahy ET,Chrysostomou V,Crowston JG

    更新日期:2016-01-01 00:00:00

  • Meibomian gland dropout in patients with dry eye disease in China.

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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Feng Y,Gao Z,Feng K,Qu H,Hong J

    更新日期:2014-10-01 00:00:00

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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Avisar I,Weinberger D,Kremer I

    更新日期:2010-02-01 00:00:00

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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Borges JM,Edward DP,Tso MO

    更新日期:1990-08-01 00:00:00

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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Johnson EI,Dunlop ME,Larkins RG

    更新日期:1999-02-01 00:00:00

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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Yue BY,Sugar J,Schrode K

    更新日期:1986-08-01 00:00:00

  • Protection of cone photoreceptor M-opsin degradation with 9-cis-β-carotene-rich alga Dunaliella bardawil in Rpe65(-/-) mouse retinal explant culture.

    abstract:PURPOSE:RPE65, a retinal pigment epithelium-specific 65-kDa protein, plays a critical role in the visual cycle of the eye. Rpe65(-/-) mice develop vision loss due to a lack of 11-cis-retinal, degradation of M-opsin and mislocalization of S-opsin. Several studies have suggested that 9-cis-β-carotene, a precursor of 9-ci...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Ozaki T,Nakazawa M,Kudo T,Hirano S,Suzuki K,Ishiguro S

    更新日期:2014-12-01 00:00:00

  • Moxifloxacin and cholesterol combined treatment of pneumococcal keratitis.

    abstract:PURPOSE:Compare the efficacy of treatment of pneumococcal keratitis with cholesterol, moxifloxacin, or a mixture of the two (moxifloxacin/cholesterol). MATERIALS AND METHODS:New Zealand white rabbits were injected intrastromally with 10(6) colony-forming units (CFU) of a clinical keratitis strain of Streptococcus pneu...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Sanders ME,Tullos NA,Taylor SD,Norcross EW,King LB,Tolo I,Marquart ME

    更新日期:2010-12-01 00:00:00

  • C5a receptor-mediated production of IL-8 by the human retinal pigment epithelial cell line, ARPE-19.

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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Fukuoka Y,Medof EM

    更新日期:2001-11-01 00:00:00

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    journal_title:Current eye research

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Papangkorn K,Truett KR,Vitale AT,Jhaveri C,Scales DK,Foster CS,Montieth A,Higuchi JW,Brar B,Higuchi WI

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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Narayanan R,Kenney MC,Kamjoo S,Trinh TH,Seigel GM,Resende GP,Kuppermann BD

    更新日期:2005-06-01 00:00:00

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    abstract::Membrane response to the various temperatures as one of the external factors was investigated in the lenses of the poikilothermal animal and the homothermal animal. The rainbow trout lens was used as the poikilothermal material and the rat lens as the homothermal material. The rainbow trout lens maintained in vitro it...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Iwata S

    更新日期:1985-04-01 00:00:00

  • Compensation for spectacle lenses involves changes in proteoglycan synthesis in both the sclera and choroid.

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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Nickla DL,Wildsoet C,Wallman J

    更新日期:1997-04-01 00:00:00

  • The Distinct Biometric Features of High Myopia Compared to Moderate Myopia.

    abstract:PURPOSE:To evaluate changes in biometric parameters in myopic eyes. MATERIALS AND METHODS:412 eyes of 412 young myopic patients underwent ophthalmic examinations including assessments of refractive error, axial length (AL), anterior chamber depth (ACD), and central corneal thickness (CCT). By using spectral domain opt...

    journal_title:Current eye research

    pub_type: 杂志文章


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    更新日期:2016-12-01 00:00:00

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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Kilic F,Trevithick JR

    更新日期:1995-10-01 00:00:00

  • Improving effects of topical administration of iganidipine, a new calcium channel blocker, on the impaired visual evoked potential after endothelin-1 injection into the vitreous body of rabbits.

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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Oku H,Sugiyama T,Kojima S,Watanabe T,Ikeda T

    更新日期:2000-02-01 00:00:00

  • Increasing cell density down-regulates the expression of acidic FGF by human RPE cells in vitro.

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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Kitaoka T,Bost LM,Ishigooka H,Aotaki-Keen AE,Hjelmeland LM

    更新日期:1993-11-01 00:00:00

  • Signs and Symptoms of Dry Eye in Keratoconus Patients Before and After Intrastromal Corneal Rings Surgery.

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    journal_title:Current eye research

    pub_type: 杂志文章


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    更新日期:2017-04-01 00:00:00

  • Hydrogen peroxide localization in ocular tissue: an electron microscopic cytochemical study.

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    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Atalla LR,Sevanian A,Rao NA

    更新日期:1988-09-01 00:00:00

  • Plasma Rich in Growth Factors for the Treatment of Ocular Surface Diseases.

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    journal_title:Current eye research

    pub_type: 杂志文章,评审


    authors: Anitua E,Muruzabal F,de la Fuente M,Merayo J,Durán J,Orive G

    更新日期:2016-07-01 00:00:00