Abstract:
Purpose:ISG15, a di-ubiquitin-like protein, is critical for controlling certain viral and bacterial infections. We sought to determine if ISG15 plays a role in corneal innate immunity against Candida albicans (C. albicans) using a C57BL/6 (B6) mouse model of human fungal keratitis. Methods:Scarified corneas of adult B6 mice were pretreated with TLR5 ligand flagellin and then inoculated with C. albicans. The expression of ISG15 and other genes involved in ISG15 conjugation (ISGylation) was determined by real-time PCR. ISG15 expression and distribution in infected corneas were assessed by immunohistochemistry. ISGylation was examined by Western blotting. siRNA knockdown and recombinant ISG15 were used to elucidate the effects of ISG15 on controlling fungal keratitis by clinical scoring, fungal number plate counting, ELISA cytokine determination, and polymorphonuclear leukocytes (PMN) infiltration measurement. Results:Heat-killed C. albicans induced expression of ISG15, and hBD2 was markedly enhanced by flagellin-pretreatment in cultured human primary corneal epithelial cells (CECs). In vivo, C. albicans infection induced the expression of ISG15, ISGylation-associated genes (UBE1L, UBCH8, and HERC5), and ISGylation in mouse CECs, all of which were enhanced by flagellin-pretreatment. siRNA knockdown of ISG15 increased keratitis severity, dampened flagellin-induced protection, and greatly suppressed the expressions of ISGylation enzymes, IFN-γ, but not CXCL2 in B6 mouse CECs. Recombinant ISG15, on the other hand, enhanced corneal innate immunity against C. albicans and suppressed infection-induced IL-1β, but not IL-Ra expression. ISG15 alone induced the expression of IL-1Ra, CXCL10, and CRAMP in mouse CECs. ISG15 was upregulated and secreted in cultured human CECs in response to challenge in a type 1 IFN-dependent manner. Conclusions:Our data, for the first time, demonstrate that ISG15 acts as an immunomodulator in the cornea and plays a critical role in controlling fungal keratitis.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Dong C,Gao N,Ross BX,Yu FXdoi
10.1167/iovs.17-21476subject
Has Abstractpub_date
2017-06-01 00:00:00pages
2948-2958issue
7eissn
0146-0404issn
1552-5783pii
2632038journal_volume
58pub_type
杂志文章abstract:PURPOSE:To test the hypothesis that acute topical dorzolamide (DZ) decreases intraocular pressure (IOP) and increases retinal and choroidal blood flow in the DBA/2J mouse model of glaucoma. METHODS:Retinal and choroidal blood flow were measured in 4- and 9-month-old DBA/2J mice, and 4-month C57BL/6 (control) mice unde...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-18291
更新日期:2016-03-01 00:00:00
abstract:PURPOSE:In situ 2-photon excitation fluorescence (TPEF) of the human trabecular meshwork (TM) reveals beams of heterogeneous autofluorescence (AF) comprising high intensity fluorescent fibers (AF-high) on a background of lower intensity fluorescence (AF-low). To determine the sources of this AF heterogeneity, we imaged...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.12-11235
更新日期:2013-07-18 00:00:00
abstract::To investigate the accumulation of tear proteins on disposable extended-wear contact lenses (42% Etafilcon A and 58% hydration), a technique involving sodium dodecyl sulfate-polyacrylamide minigel electrophoresis combined with a sensitive silver-staining method was used. Besides the binding of large amounts of tear ly...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1990-11-01 00:00:00
abstract:PURPOSE:To assess changes in rod and cone visual functions in a mouse model of Fundus albipunctatus with disrupted 11-cis-retinol dehydrogenase (RDH) genes after pharmacologic treatment with an artificial retinal chromophore. METHODS:Retinoid levels and photoreceptor functions of Rdh5-/-Rdh11-/- mice at a variety of l...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-0215
更新日期:2006-10-01 00:00:00
abstract:PURPOSE:Alkali burning of the rabbit cornea is a well-established model for the study of anterior surface inflammation, neovascularization, and wound-healing processes. 12-hydroxyeicosanoids have been implicated as mediators of such responses. 12(S)-hydroxyeicosatetraenoic acid (12[S]-HETE) is a lipoxygenase-derived ar...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract:PURPOSE:TGF-betas regulate cell proliferation and differentiation, and they play important roles in maintenance of corneal epithelium. However, the precise function of TGF-betas in the corneal epithelium remains unclear. In this study, cDNA expression array technology was used to demonstrate the effect of TGF-beta1 on ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2001-07-01 00:00:00
abstract:PURPOSE:Adipose-derived stem cells (ASCs) have gained importance due to their myriad potential clinical applications. We hypothesize that progenitor cells also exist besides those conventionally isolated from the stromal vascular fraction (SVF). METHOD:Central and medial orbital adipose tissues obtained from patients ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-14441
更新日期:2014-07-03 00:00:00
abstract::Sixteen patients with osteogenesis imperfecta (OI) have undergone a thorough eye examination. These patients had statistically significantly lower ocular rigidity measurements than a group of normal volunteers matched on age, sex, and refractive error. In addition, the corneal diameter and length of the eyeball was sm...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1981-06-01 00:00:00
abstract::The relationship between intraocular and systemic blood pressures was investigated in a prospective study of 572 middle-aged men. There was no consistent relationship between intraocular pressure at first visit and age. Subjects with an intraocular pressure greater than 20 mm Hg had a significantly higher systolic blo...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1990-11-01 00:00:00
abstract:PURPOSE:We investigated the neuroprotective effect of human serum albumin nanoparticles (HSA-NPs) and their conjugation with brimonidine (HSA-Br-NPs) on retinal ganglion cells (RGCs) in optic nerve crush (ONC) model. METHODS:We fabricated HSA-Br-NPs by ethanol precipitation, including 0.18% brimonidine (Br) and 3.5% h...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-16538
更新日期:2015-08-01 00:00:00
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
doi:10.1167/iovs.04-0212
更新日期:2005-01-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-8677
更新日期:2012-07-01 00:00:00
abstract:Purpose:To quantify and evaluate macular superficial capillaries and large vessels separately using an optical coherence tomographic angiography (OCTA)-based automatic segmentation algorithm. Methods:In this cross-sectional study, all eyes were scanned using an OCTA device with 3 × 3 mm cube centered on the fovea. Ret...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-23676
更新日期:2018-04-01 00:00:00
abstract:PURPOSE:Methionine-sulfoxide reductases are unique, in that their ability to repair oxidized proteins and MsrA, which reduces S-methionine sulfoxide, can protect lens cells against oxidative stress damage. To date, the roles of MsrB1, -B2 and -B3 which reduce R-methionine sulfoxide have not been established for any mam...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-0018
更新日期:2005-06-01 00:00:00
abstract:Purpose:Patients express their discomfort by subjective complaints, which may not clearly express the extent of their discomfort. This study noninvasively and objectively quantified ocular discomfort, a form of feeling, from the prefrontal cortex by functional near-infrared ray spectroscopy topography. Methods:This ca...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.18-24840
更新日期:2018-09-04 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2002-04-01 00:00:00
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
doi:10.1167/iovs.15-18127
更新日期:2016-04-01 00:00:00
abstract:PURPOSE:To examine the possible presence of a major gene determining susceptibility to cortical cataract. METHODS:The percentage of the lens area involved with cortical opacity, summed over both eyes, was evaluated in 1275 individuals from the Beaver Dam Eye Study. After adjusting for the effects of age and sex, these...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::The visual effects of carbon disulfide exposure were studied in macaque monkeys with measurements of visual thresholds, fluorescein angiography and fundus photography. Five monkeys were exposed by inhalation for 6 hr a day, 5 days a week to 256 ppm carbon disulfide (CS2). The motor dysfunction observed in these monkey...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1988-04-01 00:00:00
abstract:PURPOSE:Previous reports indicated that pregnancy and corneal injury (CI) trigger alterations of lacrimal gland (LG) growth factor expression and redistributions of lymphocytes from periductal foci to acini. The purpose of this study was to test our hypothesis that pregnancy would exacerbate the changes induced by CI. ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1034
更新日期:2006-04-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-12404
更新日期:2013-07-30 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.19-28063
更新日期:2019-11-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,meta分析,评审
doi:10.1167/iovs.07-1501
更新日期:2008-12-01 00:00:00
abstract:PURPOSE:Macular corneal dystrophy (MCD) is a rare corneal dystrophy that is characterized by abnormal deposits in the corneal stroma, keratocytes, Descemet's membrane, and endothelium, accompanied by progressive clouding. It has been classified into three immunophenotypes--MCD types I, IA, and II--according to the seru...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2002-02-01 00:00:00
abstract:PURPOSE:Neural ectopic rewiring in retinal degeneration such as retinitis pigmentosa (RP) may form functional synapses between cones and rod bipolar cells that cause atypical signal processing. In this study, the multifocal electroretinograms (mfERGs) of a large animal model of RP, the rhodopsin P347L transgenic (Tg) p...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-1159
更新日期:2008-05-01 00:00:00
abstract:PURPOSE:To determine the age of onset of the pupil grating response (PGR). To compare estimates of resolution acuity obtained by pupillometric and behavioral methods in early infancy. METHODS:Dynamic infrared pupillometry was undertaken on 19 newborn infants while they fixated a uniform background upon which a 0.1 c/d...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract:PURPOSE:Focal opacities are signs of early cataractogenesis in the human lens. They progress slowly over a lifetime and may be precursors of mature cataracts. The authors analyzed changes in proteins, phospholipids, and cholesterol in these opacities using in situ techniques: Raman microspectroscopy, filipin cytochemis...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.19-26894
更新日期:2019-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1492
更新日期:2006-07-01 00:00:00
abstract::Isotonic, neutral buffered solutions of benzalkonium chloride or chlorhexidine digluconate were applied topically to one eye of rabbits or human subjects. Contralateral control eyes received phosphate buffered saline as placebo. One-half hour later, the tear film of both eyes was loaded with nonpreserved sodium fluore...
journal_title:Investigative ophthalmology & visual science
pub_type: 临床试验,杂志文章
doi:
更新日期:1984-12-01 00:00:00