IFT81 as a Candidate Gene for Nonsyndromic Retinal Degeneration.


Purpose:IFT81, a core component of the IFT-B complex, involved in the bidirectional transport of ciliary proteins, has been recently implicated in syndromic ciliopathies. However, none of the IFT-B core complex proteins have been associated with nonsyndromic retinal dystrophies. Given the importance of ciliary transport in photoreceptor function and structural maintenance, we sought to investigate the impact of IFT (intraflagellar transport) mutations in nonsyndromic retinopathies. Methods:Whole exome sequencing was performed on 50 cone-rod dystrophy (CRD) patients that were previously screened for mutations in known retinal disease genes. The impact of candidate mutation was studied using in vitro cell system and in vivo zebrafish assay to determine the pathogenicity of the variant. Results:Compound heterozygous mutations in IFT81, including one nonsense (c.1213C>T, p.R405*) and one missense variant (c.1841T>C, p.L614P), were identified in a nonsyndromic CRD proband. Extensive functional analyses of the missense variant in cell culture and zebrafish strongly suggests its pathogenic nature. Loss of IFT81 impairs ciliogenesis and, interestingly, the missense variant displayed significantly reduced rescue of ciliogenesis in the IFT81 knockdown in vitro system. Consistently, dramatic reduction of rescue efficiency of the ift81 mutant zebrafish embryo by mRNA with the missense variant was observed, further supporting its pathogenicity. Conclusions:Consistent with the function of the IFT-B complex in the maintenance of photoreceptor cilium, we report a case of mutations in a core IFT-B protein, IFT81. This represents the first report of mutations in IFT81 as a candidate gene for nonsyndromic retinal dystrophy, hence expanding the phenotype spectrum of IFT-B components.


Dharmat R,Liu W,Ge Z,Sun Z,Yang L,Li Y,Wang K,Thomas K,Sui R,Chen R




Has Abstract


2017-05-01 00:00:00














  • Assessment of central visual function in Stargardt's disease/fundus flavimaculatus with ultrahigh-resolution optical coherence tomography.

    abstract:PURPOSE:To assess photoreceptor morphology in patients with Stargardt's disease and fundus flavimaculatus using ultrahigh-resolution optical coherence tomography (UHR-OCT) and correlate it with visual acuity (VA). METHODS:This was a prospective observational case series. Fourteen patients with Stargardt's disease (nin...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Ergun E,Hermann B,Wirtitsch M,Unterhuber A,Ko TH,Sattmann H,Scholda C,Fujimoto JG,Stur M,Drexler W

    更新日期:2005-01-01 00:00:00

  • Controlled Release of Dexamethasone From an Intravitreal Delivery System Using Porous Silicon Dioxide.

    abstract:PURPOSE:The current study aims to evaluate a porous silicon-based drug delivery system meant for sustained delivery of dexamethasone (Dex) to the vitreous and retina. METHODS:Dexamethasone was grafted covalently into the pore walls of fully oxidized porous silicon particles (pSiO2-COO-Dex), which then was evaluated fo...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Hou H,Wang C,Nan K,Freeman WR,Sailor MJ,Cheng L

    更新日期:2016-02-01 00:00:00

  • Selective blockade of cytoskeletal actin remodeling reduces experimental choroidal neovascularization.

    abstract:PURPOSE:The efficacy of the peptide Ac-EEED on reducing cell adhesion and proliferation in vitro and choroidal neovascularization (CNV) in vivo was examined. METHODS:The peptide chimera containing the Ac-EEED sequence was chemically linked to the N terminus of the XMTM delivery peptide from the E(rns) viral surface pr...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Caballero S,Yang R,Grant MB,Chaqour B

    更新日期:2011-04-16 00:00:00

  • Rapid upregulation of fibroblast growth factor receptor 1 (flg) by rat photoreceptor cells after injury.

    abstract:PURPOSE:To determine the mechanism by which basic fibroblast growth factor (bFGF) exerts its neuroprotective effects on degenerating or injured photoreceptors. METHODS:Confocal immunofluorescence microscopy was used to identify sites of bFGF and FGF receptor 1 (FGFR1) expression after focal injury or experimental reti...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Ozaki S,Radeke MJ,Anderson DH

    更新日期:2000-02-01 00:00:00

  • ATP-induced photoreceptor death in a feline model of retinal degeneration.

    abstract:PURPOSE:To develop and characterize a feline model of retinal degeneration induced by intravitreal injection of adenosine triphosphate (ATP). METHODS:Nineteen normally sighted adult cats received 100 μL intravitreal injections of ATP with a final concentration of 11, 22, or 55 mM at the retina. Four animals were eutha...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Aplin FP,Luu CD,Vessey KA,Guymer RH,Shepherd RK,Fletcher EL

    更新日期:2014-11-25 00:00:00

  • Inhibition of human scleral fibroblast cell attachment to collagen type I by TGFBIp.

    abstract:PURPOSE:Transforming growth factor beta-induced protein (TGFBIp; 68 kDa) is a secreted extracellular matrix (ECM) protein that has been demonstrated to regulate cell attachment in a variety of cell types. The sclera synthesizes and secretes TGFBIp, which may function to facilitate scleral ECM remodeling events associat...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Shelton L,Rada JA

    更新日期:2009-08-01 00:00:00

  • Photoreceptor Degeneration Accompanies Vascular Changes in a Zebrafish Model of Diabetic Retinopathy.

    abstract:Purpose:Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness worldwide in the working-age population, and the incidence is rising. Until now it has been difficult to define initiating events and disease progression at the molecular level, as available diabetic rodent models do not present the...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Ali Z,Zang J,Lagali N,Schmitner N,Salvenmoser W,Mukwaya A,Neuhauss SCF,Jensen LD,Kimmel RA

    更新日期:2020-02-07 00:00:00

  • Activation of signaling pathways and stress-response genes in an experimental model of retinal detachment.

    abstract:PURPOSE:Despite the high metabolic demands of the neural retina, its detachment from the retinal pigment epithelium does not lead to immediate death for most of the cells. This study was undertaken to test the hypothesis that intrinsic protective mechanisms are activated in the neural retina during early stages of reti...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Zacks DN,Han Y,Zeng Y,Swaroop A

    更新日期:2006-04-01 00:00:00

  • Macular pigment optical density in young adults of South Asian origin.

    abstract:PURPOSE:To assess the range of macular pigment optical density (MPOD) in a healthy group of young adults of South Asian origin; to investigate whether any dietary factors or personal characteristics were related to intersubject variations in MPOD; and to compare the mean MPOD of the South Asian group with the mean MPOD...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Howells O,Eperjesi F,Bartlett H

    更新日期:2013-04-17 00:00:00

  • Difluprednate 0.05% versus prednisolone acetate 1% for endogenous anterior uveitis: a phase III, multicenter, randomized study.

    abstract:PURPOSE:Endogenous anterior uveitis (AU), when untreated, may lead to vision loss. This study compared the safety and efficacy of difluprednate versus prednisolone acetate for the treatment of this condition. METHODS:This phase III, double-masked, noninferiority study randomized patients with mild to moderate endogeno...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Sheppard JD,Toyos MM,Kempen JH,Kaur P,Foster CS

    更新日期:2014-05-06 00:00:00

  • Test-Retest Repeatability of Microperimetry at the Border of Deep Scotomas.

    abstract:PURPOSE:The purpose of this study was to examine the test-retest repeatability of microperimetric sensitivity at the border of deep scotomas. METHODS:Thirty normal participants underwent two examinations, each on the Macular Integrity Assessment (MAIA) microperimeter and on the MP-1 microperimeter (four examinations i...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Wu Z,Jung CJ,Ayton LN,Luu CD,Guymer RH

    更新日期:2015-04-01 00:00:00

  • Inner Retinal Oxygen Delivery, Metabolism, and Extraction Fraction in Ins2Akita Diabetic Mice.

    abstract:Purpose:Retinal nonperfusion and hypoxia are important factors in human diabetic retinopathy, and these presumably inhibit energy production and lead to cell death. The purpose of this study was to elucidate the effect of diabetes on inner retinal oxygen delivery and metabolism in a mouse model of diabetes. Methods:Ph...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Blair NP,Wanek J,Felder AE,Brewer KC,Joslin CE,Shahidi M

    更新日期:2016-11-01 00:00:00

  • Directional bias of neurons in V1 and V2 of strabismic monkeys: temporal-to-nasal asymmetry?

    abstract:PURPOSE:Strabismus that develops shortly after birth is known to cause temporal-to-nasal eye movement asymmetries under monocular viewing. The neural mechanisms underlying this deficit are not well understood. In the current study, the hypothesis that this eye movement anomaly reflects a similar asymmetry in the direct...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Watanabe I,Bi H,Zhang B,Sakai E,Mori T,Harwerth RS,Smith EL 3rd,Chino YM

    更新日期:2005-10-01 00:00:00

  • MicroRNA-328 may influence myopia development by mediating the PAX6 gene.

    abstract:PURPOSE:We showed previously that single nucleotide polymorphism (SNP) rs662702 in PAX6 may be located in a microRNA-328 binding site that causes susceptibility to high myopia. Our study was done to elucidate the role of PAX6 and its relationship with microRNA-328 in myopia. METHODS:A luciferase assay was used to conf...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Chen KC,Hsi E,Hu CY,Chou WW,Liang CL,Juo SH

    更新日期:2012-05-31 00:00:00

  • Correlation of OCT characteristics and retinal sensitivity in neovascular age-related macular degeneration in the course of monthly ranibizumab treatment.

    abstract:PURPOSE:To evaluate the functional treatment response 3 months and 12 months after monthly ranibizumab in neovascular age-related macular degeneration (NAMD). METHODS:Twenty-six eyes showing treatment-naïve NAMD were examined with the Heidelberg Spectralis OCT (SD-OCT) and the Nidek MP-1 microperimeter (MP) at baselin...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 临床试验,杂志文章


    authors: Sulzbacher F,Kiss C,Kaider A,Roberts P,Munk M,Kroh ME,Sayegh R,Schmidt-Erfurth U

    更新日期:2013-02-01 00:00:00

  • Electroretinographic anomalies in mice with mutations in Myo7a, the gene involved in human Usher syndrome type 1B.

    abstract:PURPOSE:In humans, mutations in the gene encoding myosin VIIa can cause Usher syndrome type 1b (USH1B), a disease characterized by deafness and retinitis pigmentosa. Myosin VIIa is also the gene responsible for the inner ear abnormalities at the shaker1 (sh1) locus in mice. To date, none of the sh1 alleles examined hav...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Libby RT,Steel KP

    更新日期:2001-03-01 00:00:00

  • Blue Multifocal Pupillographic Objective Perimetry in Glaucoma.

    abstract:PURPOSE:This study investigated multifocal pupillographic objective perimetry (mfPOP) stimuli that target the intrinsic photosensitivity of melanopsin retinal ganglion cells. The diagnostic potential for glaucoma is compared between stimuli biased toward either cone input to these cells or their melanopsin response. M...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Carle CF,James AC,Kolic M,Essex RW,Maddess T

    更新日期:2015-10-01 00:00:00

  • Neural reprogramming in retinal degeneration.

    abstract:PURPOSE:Early visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased remodeling of the neural retina. The authors sought to explore the functional expression of ionotropic (iGluR) and group 3, type 6 metabotropic (mGluR6) glutamate receptors in late-stage photoreceptor degenerat...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Marc RE,Jones BW,Anderson JR,Kinard K,Marshak DW,Wilson JH,Wensel T,Lucas RJ

    更新日期:2007-07-01 00:00:00

  • Age and topographic variation of insulin-like growth factor-binding protein 2 in the human rpe.

    abstract:PURPOSE:Previous studies have shown that insulin-like growth factor-binding protein (IGFBP)-2 is markedly upregulated in senescent RPE cells in vitro, and might therefore be a marker of senescent cells in vivo. This study was conducted to determine whether IGFBP-2 expression in human RPE cells from the macula and perip...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Miyamura N,Mishima K,Honda S,Aotaki-Keen AE,Morse LS,Handa JT,Hjelmeland LM

    更新日期:2001-06-01 00:00:00

  • Genotype-phenotype correlation of mouse pde6b mutations.

    abstract:PURPOSE:To identify the underlying molecular defects causing retinal degeneration in seven N-ethyl-N-nitrosourea (ENU) induced mutant alleles of the Pde6b gene and to analyze the timescale of retinal degeneration in these new models of retinitis pigmentosa. METHODS:Conformation sensitive capillary electrophoresis and ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Hart AW,McKie L,Morgan JE,Gautier P,West K,Jackson IJ,Cross SH

    更新日期:2005-09-01 00:00:00

  • Secretory component of IgA: a marker for differentiation of ocular epithelium.

    abstract::Secretory component (SC) was studied by indirect immunofluorescence of the ocular surface epithelium. We find that conjunctival epithelium produces this component, and that it is absent in the corneal epithelium. Conjunctival epithelium loses its SC staining within 1 to 2 days as it grows over a denuded corneal stroma...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Liu SH,Tagawa Y,Prendergast RA,Franklin RM,Silverstein AM

    更新日期:1981-01-01 00:00:00

  • Anti-Inflammatory Effect of Dexamethasone Controlled Released From Anterior Suprachoroidal Polyurethane Implants on Endotoxin-Induced Uveitis in Rats.

    abstract:PURPOSE:Targeted drug delivery to the ocular tissues remains a challenge. Biodegradable intraocular implants allow prolonged controlled release of drugs directly into the eye. In this study, we evaluated an anterior suprachoroidal polyurethane implant containing dexamethasone polyurethane dispersions (DX-PUD) as a drug...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Barbosa Saliba J,Vieira L,Fernandes-Cunha GM,Rodrigues Da Silva G,Ligório Fialho S,Silva-Cunha A,Bousquet E,Naud MC,Ayres E,Oréfice RL,Tekaya M,Kowalczuk L,Zhao M,Behar-Cohen F

    更新日期:2016-04-01 00:00:00

  • Porous poly(ε-caprolactone) scaffolds for retinal pigment epithelium transplantation.

    abstract:PURPOSE:Retinal pigment epithelium (RPE) transplantation is a promising strategy for the treatment of dry age-related macular degeneration (AMD). However, previous attempts at subretinal RPE cell transplantation have experienced limited success due to poor adhesion, organization, and function on aged or diseased Bruch'...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: McHugh KJ,Tao SL,Saint-Geniez M

    更新日期:2014-03-25 00:00:00

  • Comparison of risk factors for bilateral and unilateral eye involvement in normal-tension glaucoma.

    abstract:PURPOSE:To compare the risk factors for bilateral and unilateral disease in normal-tension glaucoma (NTG). METHODS:The study analyzed data from consecutive NTG patients with either bilateral (n = 194) or unilateral (n = 193) disease. Multivariate regression models were used to evaluate the following potential risk fac...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Kim C,Kim TW

    更新日期:2009-03-01 00:00:00

  • Regional Differences and Physiologic Behaviors in Peripapillary Scleral Fibroblasts.

    abstract:Purpose:The purpose of this study was to describe the cellular architecture of normal human peripapillary sclera (PPS) and evaluate surface topography's role in fibroblast behavior. Methods:PPS cryosections from nonglaucomatous eyes were labelled for nuclei, fibrillar actin (FA), and alpha smooth muscle actin (αSMA) a...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Szeto J,Chow A,McCrea L,Mozzer A,Nguyen TD,Quigley HA,Pitha I

    更新日期:2021-01-04 00:00:00

  • Atlas of Human Retinal Pigment Epithelium Organelles Significant for Clinical Imaging.

    abstract:Purpose:To quantify organelles impacting imaging in the cell body and intact apical processes of human retinal pigment epithelium (RPE), including melanosomes, lipofuscin-melanolipofuscin (LM), mitochondria, and nuclei. Methods:A normal perifovea of a 21-year-old white male was preserved after rapid organ recovery. An...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Pollreisz A,Neschi M,Sloan KR,Pircher M,Mittermueller T,Dacey DM,Schmidt-Erfurth U,Curcio CA

    更新日期:2020-07-01 00:00:00

  • Origin and biosynthesis of human tear fluid proteins.

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    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Janssen PT,van Bijsterveld OP

    更新日期:1983-05-01 00:00:00

  • Tumor-infiltrating macrophages (CD68(+) cells) and prognosis in malignant uveal melanoma.

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    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Mäkitie T,Summanen P,Tarkkanen A,Kivelä T

    更新日期:2001-06-01 00:00:00

  • Discovery of a Cynomolgus Monkey Family With Retinitis Pigmentosa.

    abstract:Purpose:To accelerate the development of new therapies, an inherited retinal degeneration model in a nonhuman primate would be useful to confirm the efficacy in preclinical studies. In this study, we describe the discovery of retinitis pigmentosa in a cynomolgus monkey (Macaca fascicularis) pedigree. Methods:First, sc...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Ikeda Y,Nishiguchi KM,Miya F,Shimozawa N,Funatsu J,Nakatake S,Fujiwara K,Tachibana T,Murakami Y,Hisatomi T,Yoshida S,Yasutomi Y,Tsunoda T,Nakazawa T,Ishibashi T,Sonoda KH

    更新日期:2018-02-01 00:00:00

  • Directed Differentiation of Human Corneal Endothelial Cells From Human Embryonic Stem Cells by Using Cell-Conditioned Culture Media.

    abstract:Purpose:A shortage of human corneal endothelial cells (HCEC) for transplant and current methods of differentiation induction require chemical compounds, which might cast further influences after differentiation induction. Therefore, we developed a simple and straightforward approach to endothelial cell differentiation ...

    journal_title:Investigative ophthalmology & visual science

    pub_type: 杂志文章


    authors: Chen X,Wu L,Li Z,Dong Y,Pei X,Huang Y,Wang L

    更新日期:2018-06-01 00:00:00