Direct comparison of administration routes for AAV8-mediated ocular gene therapy.


PURPOSE:We recently demonstrated that direct subretinal (SR) injection of adeno-associated virus (AAV) type 8 (AAV8) into photoreceptor cells and retinal pigment epithelium (RPE) is a highly efficient model of gene delivery. The current study compared transduction efficiency and expression patterns associated with various routes of vector administration. METHOD:The efficacy of intravitreal (VT), SR and subconjunctival (SC) injections for delivery of AAV8-derived vectors, i.e. those expressing luciferase (Luc) and enhanced green fluorescent protein (GFP) - AAV8/Luc and AAV8/GFP, respectively - were compared in an animal (mouse) model (n = 8 mice/group). Transduction efficiency and expression patterns were examined at post-injection weeks 1 and 2, and months 1, 3, 6 and 12 via in vivo imaging. RESULTS:One year after AAV injection, AAV8/Luc-treated mice exhibited stable and sustained high expression of vector in the VT and SR groups, but not in the SC group (VT:SR:SC = 3,218:2,923:115; 1 × 10(5 )photons/s). Histological analysis showed that GFP expression was observed in the inner retina of VT group mice, and in photoreceptor cells and RPE of SR group mice, whereas no GFP expression was noted in the SC group. Electroretinography (ERG) revealed adverse effects following SR delivery. CONCLUSIONS:Results suggest that both SR and VT injections of AAV8 vectors are useful routes for administering ocular gene therapy, and stress the importance of selecting an appropriate administration route, i.e. one that targets specific cells, for treating ocular disorders.


Curr Eye Res


Current eye research


Igarashi T,Miyake K,Asakawa N,Miyake N,Shimada T,Takahashi H




Has Abstract


2013-05-01 00:00:00












  • Intramuscular Distribution of the Abducens Nerve in the Lateral Rectus Muscle for the Management of Strabismus.

    abstract:AIMS:To elucidate the intramuscular distribution and branching patterns of the abducens nerve in the lateral rectus (LR) muscle so as to provide anatomical confirmation of the presence of compartmentalization, including for use in clinical applications such as botulinum toxin injections. METHODS:Thirty whole-mount hum...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Shin HJ,Lee SH,Shin KJ,Koh KS,Song WC

    更新日期:2018-06-01 00:00:00

  • Optimization of Cultured Human Corneal Endothelial Cell Sheet Transplantation and Post-Operative Sheet Evaluation in a Rabbit Model.

    abstract:PURPOSE:To optimize cultured human corneal endothelial cell (cHCEC) sheet transplantation technique for maintenance of cHCEC viability. MATERIALS AND METHODS:cHCEC sheets cultured on a collagen scaffold were covered with or without Viscoat® and exposed to humidified air in the incubator. cHCEC sheets with or without V...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Yamaguchi M,Shima N,Kimoto M,Ebihara N,Murakami A,Yamagami S

    更新日期:2016-09-01 00:00:00

  • Nicotine treatment alters NF-kappaB expression in human cytomegalovirus-infected ARPE-19 cells.

    abstract:PURPOSE:To test if nicotine counteracts the dampening effect of human cytomegalovirus (HCMV) infection of NF-kappaB in retinal pigment epithelial (RPE) cells, thereby increasing the permissiveness of RPE cells for HCMV replication. METHODS:Human ARPE-19 cells were transfected with NF-kappaB luciferase DNA, inoculated ...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Buckner AE,Dix RD

    更新日期:2006-02-01 00:00:00

  • Xenobiotic- and Serum-Free Culture of Oral Mucosal Epithelial Cells on Contact Lenses.

    abstract:PURPOSE/AIM:Cultured autologous oral mucosal epithelial cells (OMECs) have proven useful in the treatment of ocular surface disorders. This study is the first to investigate the potential of expanding OMEC in a xenobiotic- and serum-free medium using therapeutic contact lenses (CLs) as a substrate and carrier. MATERIA...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Björkblom B,Eidet JR,Utheim TP,Ulltveit-Moe HF,Raeder S

    更新日期:2016-01-01 00:00:00

  • Altered Functional Connectivity of the Primary Visual Cortex in Adult Comitant Strabismus: A Resting-State Functional MRI Study.

    abstract:PURPOSE:The aim of this study was to examine the functional connectivity between the primary visual cortex and other cortical areas during rest in normal subjects and patients with comitant strabismus using functional magnetic resonance imaging (fMRI). METHODS:A prospective, observational study was conducted. Ten pati...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Yan X,Wang Y,Xu L,Liu Y,Song S,Ding K,Zhou Y,Jiang T,Lin X

    更新日期:2019-03-01 00:00:00

  • Normal expression levels of cathepsins, protease inhibitors, and Sp1 in conjunctival tissues from patients with keratoconus.

    abstract:PURPOSE:In keratoconus corneas, it has been shown that levels of degradative enzymes and transcription factor Sp1 are elevated and those of inhibitors are reduced, especially in the epithelial layer. This study is to determine whether the biochemical abnormalities identified in corneas also exist in conjunctival tissue...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Maruyama I,Zhou L,Sugar J,Yue BY

    更新日期:2000-11-01 00:00:00

  • An Experimental Animal Model of Photodynamic Optic Nerve Head Injury (PONHI).

    abstract:PURPOSE:Anterior ischemic optic neuropathy (AION) is the most common cause of non-glaucomatous optic nerve head (ONH) injury among older adults. AION results from a sudden ischemic insult to the proximal portion of the optic nerve, typically leading to visual impairment. Here, we present an experimental model of photod...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Mantopoulos D,Bouzika P,Tsakris A,Pawlyk BS,Sandberg MA,Miller JW,Rizzo Iii JF,Vavvas DG,Cestari DM

    更新日期:2016-11-01 00:00:00

  • Rapid detection of herpes simplex virus (HSV) antigen in human ocular infections.

    abstract::The new HERPCHEK (Dupont, No. Billerica, MA) enzyme immunosorbent assay (EIA) was used in a double-blind clinical study for rapid and specific detection of ocular herpes simplex virus (HSV) infection. This 4-hour assay can be used to demonstrate conclusively the presence of HSV antigen without culture and thereby rapi...

    journal_title:Current eye research

    pub_type: 临床试验,杂志文章


    authors: Dunkel EC,Pavan-Langston D,Fitzpatrick K,Cukor G

    更新日期:1988-07-01 00:00:00

  • Peroxynitrite-induced apoptosis in photoreceptor cells.

    abstract:PURPOSE:To study the mechanisms of peroxynitrite-induced photoreceptor cell damage, using retinal cultures and a peroxynitrite donor, 3-morpholinosydnonimine (SIN-1). METHODS:Retinal explants obtained from 20-day-old Lewis rat pups, were exposed to SIN-1 for varying lengths of time at varying concentrations. Apoptosis...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Ito S,Wu GS,Kimoto T,Hisatomi T,Ishibashi T,Rao NA

    更新日期:2004-01-01 00:00:00

  • Efficacy of 9-(2-phosphonylmethoxyethyl)adenine in the therapy of TK+ and TK- herpes simplex virus experimental keratitis.

    abstract::The acyclic nucleoside phosphonate analogue PMEA [9-(2-phosphonylmethoxyethyl)adenine] is a broad spectrum antiviral agent effective against DNA viruses and retroviruses. It is particularly active against the human immunodeficiency virus and, like other phosphonylmethoxyalkyl derivatives, it also inhibits HSV-1, TK- H...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Maudgal PC,De Clercq E

    更新日期:1991-01-01 00:00:00

  • Identification of two of the major phosphorylated polypeptides of the bovine lens utilizing a lens cAMP-dependent protein kinase system.

    abstract::Two of the major in vitro phosphorylated polypeptides of the bovine lens have been identified. Analysis by means of two-dimensional gel electrophoresis (IEF) has demonstrated that the lens phosphorylated 57,000 and 43,000 dalton polypeptides correspond in mobility to purified phosphorylated bovine lens vimentin and ch...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Sredy J,Roy D,Spector A

    更新日期:1984-12-01 00:00:00

  • Aberrant Epigenetic Alterations of Glutathione-S-Transferase P1 in Age-Related Nuclear Cataract.

    abstract:PURPOSE:Oxidative damage of lens tissue contributes to the formation of age-related cataract. Pi-class glutathione-S-transferase (GSTP1) plays a role in the removal of oxidative adducts by transferring them to glutathione. To assess epigenetic regulation of GSTP1 and its potential role in age-related nuclear cataract (...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Chen J,Zhou J,Wu J,Zhang G,Kang L,Ben J,Wang Y,Qin B,Guan H

    更新日期:2017-03-01 00:00:00

  • Effect of acute increases of intraocular pressure on corneal pachymetry in eyes treated with travoprost: an animal study.

    abstract:PURPOSE:To evaluate "in vivo" the effect of topical travoprost on the central corneal thickness (CCT) of rabbit eyes, and the changes in the CCT after acute increases of intraocular pressure (IOP) in these eyes. MATERIALS AND METHODS:This is an interventional, prospective, case-control, masked study. Topical travopros...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Bolívar G,Teus M,Arranz-Marquez E

    更新日期:2011-11-01 00:00:00

  • EAAT and Xc⁻ Exchanger Inhibition Depletes Glutathione in the Transformed Human Lens Epithelial Cell Line SRA 01/04.

    abstract:PURPOSE:Maintaining the high glutathione (GSH; tripeptide of glutamate, cysteine and glycine) levels in the lens cortex promotes lens health. The role of glutamate/aspartate (Glu/Asp) transporters and the cystine (Cys)/Glu exchanger (Xc(-) exchanger) in maintaining GSH in transformed human lens epithelial cells (SRA 01...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Langford MP,Redens TB,Liang C,Kavanaugh AS,Texada DE

    更新日期:2016-01-01 00:00:00

  • Relationship between Aquaporin-1 Protein Expression and Choroidal Thickness during the Recovery of Form-deprivation Myopia in Guinea Pigs.

    abstract::Purpose: The purpose of this study was to investigate the relationship between aquaporin-1 (AQP-1) protein expression in the choroid and choroid thickness (CT) during the recovery of form-deprivation (FD) myopia in guinea pigs.Materials and Methods: Seventy-two guinea pigs were randomly assigned to the normal control ...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Chen W,Zhang H,Zhang Y,Wang Q,Wang Y,Li ZW

    更新日期:2020-06-01 00:00:00

  • The upregulation of angiogenic gene expression in cultured retinal pigment epithelial cells grown on type I collagen.

    abstract:PURPOSE:Increases in matrix proteins, such as type I collagen and fibronectin, are observed with aging in the retinal pigment epithelium (RPE) basement membrane. However, little is known about altered gene expression profiles of RPE associated with increases in matrix proteins. We investigated changes in gene expressio...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Imai H,Honda S,Kondo N,Ishibashi K,Tsukahara Y,Negi A

    更新日期:2007-10-01 00:00:00

  • Femtosecond laser-assisted retinal imaging and ablation: experimental pilot study.

    abstract:PURPOSE:To investigate retinal imaging and ablation using femtosecond laser pulses. MATERIALS AND METHODS:Two non-amplified near-infrared femtosecond lasers were used to irradiate porcine retinal specimens in vitro. The lasers were used for tissue removal as well as multiphoton laser scanning microscopy. RESULTS:Abla...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Hild M,Krause M,Riemann I,Mestres P,Toropygin S,Löw U,Brückner K,Seitz B,Jonescu-Cuypers C,König K

    更新日期:2008-04-01 00:00:00

  • Localization of nitric oxide synthase isoforms in porcine ocular tissues.

    abstract:PURPOSE:To determine by immunohistochemistry the distribution of different nitric oxide synthases (NOS) isoforms in the porcine eye. METHODS:By light microscopy (immunofluorescence), porcine ocular tissues were investigated using monoclonal antibodies against neuronal NOS (nNOS; NOS I), endothelial NOS (ecNOS; NOS III...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Meyer P,Champion C,Schlötzer-Schrehardt U,Flammer J,Haefliger IO

    更新日期:1999-05-01 00:00:00

  • Corneal endothelial cells block T cell proliferation, but not T cell activation or responsiveness to exogenous IL-2.

    abstract::We previously reported that Ia+ monolayers of LEW rat corneal endothelial (CE) cells were unable to stimulate proliferation of MHC compatible T cell lines or IL-2 release from hybridomas, and inhibited [3H]-thymidine incorporation when added to conventional lymphocyte proliferation assays. Our purpose was to further a...

    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

  • Small optic cup sizes among women using tamoxifen: assessment with scanning laser ophthalmoscopy.

    abstract:PURPOSE:There is a substantial literature showing that the selective estrogen receptor modulator tamoxifen can block swelling-activated chloride channels, such as those in astrocytes. This study aimed to test the hypothesis that anatomic characteristics consistent with swelling may be measured within the optic nerve he...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Eisner A,O'Malley JP,Incognito LJ,Toomey MD,Samples JR

    更新日期:2006-04-01 00:00:00

  • Sodium/potassium ATPase in normal and cataractous human lenses.

    abstract::Na/K ATPase activity has been determined in normal and cataractous human lenses using labeled ATP as a substrate. The enzyme is distributed throughout the lens with approximately 1/3 of the total activity in the capsule-epithelium and 1/2 of the activity in the cortex. Furthermore, the activity of Na/K ATPase decrease...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Kobatashi S,Roy D,Spector A

    更新日期:1982-01-01 00:00:00

  • Collector Channels: Role and Evaluation in Schlemm's Canal Surgery.

    abstract:OBJECTIVES:1) To elucidate the role of collector channels in the aqueous humor outflow pathway 2) To suggest anatomic and functional methods of imaging collector channels in-vitro and in-vivo and 3) To discuss the role of such imaging modalities in the surgical management of glaucoma. METHODS:A thorough literature sea...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: M Elhusseiny A,Jamerson EC,Menshawey R,Tam EK,El Sayed YM

    更新日期:2020-10-01 00:00:00

  • The Effect of Antiamoebic Agents on Viability, Proliferation and Migration of Human Epithelial Cells, Keratocytes and Endothelial Cells, In Vitro.

    abstract:PURPOSE:To analyze the effect of diamidines (hexamidine-diisethionat (HD), propamidin-isethionate (PD), dibromopropamidine-diisethionat (DD)), and biguanides (polyhexamethylen biguanid (PHMB), chlorhexidine (CH)) on human corneal epithelial cell, keratocyte and endothelial cell viability, proliferation, and migration, ...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Shi L,Stachon T,Seitz B,Wagenpfeil S,Langenbucher A,Szentmáry N

    更新日期:2018-06-01 00:00:00

  • Increased catalase levels and hypoxanthine-enhanced nitro-blue tetrazolium staining in rat retina after ischemia followed by recirculation.

    abstract::In the present study, using retinal ischemia as a model, we examined if different periods of ischemia and recirculation influenced the generation of reactive oxygen species, i.e. in hydrogen peroxide generation and nitroblue tetrazolium (NBT) reduction. Ischemia was induced for 30 and 90 min by ligation of the optic n...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Zhang H,Agardh CD,Agardh E

    更新日期:1995-01-01 00:00:00

  • Ultrastructural immunocytochemical localization of herpes simplex virus (type 1) in trigeminal ganglion neurons.

    abstract::Four days after corneal inoculation of mice with herpes simplex (type 1) virus (HSV), infected trigeminal ganglion cells with and without calcitonin gene-related peptide (CGRP) antigenicity were examined by electron microscopy in sections treated with colloidal gold labeled antibodies. Cells that contain CGRP were ide...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: LaVail JH,Meade LB,Dawson CR

    更新日期:1991-01-01 00:00:00

  • Association of Tear Film Stability and Corneal Surface Temperature in Pudong Patients.

    abstract:OBJECTIVE:To investigate the association between corneal temperature on ocular surface and stability of tear film, and define the normal reference range of corneal surface temperature in the population of Pudong New Area, Shanghai, China. METHODS:Temperature of cornea (TOC) and tear film break-up time (BUT) were measu...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Yang W,Zhang L

    更新日期:2017-05-01 00:00:00

  • Effects of subconjunctival injection of mitomycin-C on iridial circulation in rabbits.

    abstract:PURPOSE:To determine the effects of a subconjunctival injection of mitomycin-C (MMC) on iridial circulation in rabbits. METHODS:Dutch rabbits anesthetized with pentobarbital received a 0.2-ml subconjunctival injection of 0.4 mg/ml or 0.1 mg/ml MMC; the contralateral eye received 0.2 ml physiological saline. Intraocula...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Tomidokoro A,Araie M,Tamaki Y,Muta K

    更新日期:1999-08-01 00:00:00

  • Pathologic changes in the retinal pigment epithelium and Bruch's membrane of fat-fed atherogenic mice.

    abstract:PURPOSE:Due to a possible link in humans between atherosclerosis, a high-fat diet, and the development of age-related retinal degenerations, we investigated retinal changes with age and diet in high-fat-fed C57BL/6 mice, a mouse model of human atherosclerosis. METHODS:We fed C57BL/6J mice either a normal chow diet or ...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Miceli MV,Newsome DA,Tate DJ Jr,Sarphie TG

    更新日期:2000-01-01 00:00:00

  • Identification of Feeder Vessels in Ocular Surface Neoplasia Using Indocyanine Green Angiography.

    abstract:PURPOSE:To evaluate indocyanine green angiography (ICGA) for the identification and characterization of afferent (feeding) and efferent (draining) vessels in patients with ocular surface neoplasia. MATERIALS AND METHODS:Consecutive patients with biopsy-proven benign, pre-invasive, or invasive ocular surface tumors of ...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Brunner M,Steger B,Romano V,Hodson M,Zheng Y,Heimann H,Kaye SB

    更新日期:2018-02-01 00:00:00

  • A low conductance chloride channel in the basolateral membranes of the non-pigmented ciliary epithelium of the rabbit eye.

    abstract:PURPOSE:Chloride efflux plays an important role in aqueous humor production. Chloride currents have been described in bovine non-pigmented ciliary epithelium (NPE), in transformed cultured human NPE, and in bovine volume-activated chloride channels described in the latter. It is the basolateral membranes of the NPE of ...

    journal_title:Current eye research

    pub_type: 杂志文章


    authors: Chen S,Sears M

    更新日期:1997-07-01 00:00:00