Abstract：
PURPOSE:α-Crystallins are small heat shock proteins that regulate cellular damage and cell survival. Expression of the proteins of the crystallin superfamily in the retina and their role in neuronal cell survival were investigated in two animal models of diabetes and retinal neurons in culture. METHODS:Crystallin expression was assessed in streptozotocin-induced and Ins2(Akita) diabetic mice using iTRAQ methodology and validated using immunoblotting. Protein-protein interactions, solubility properties, and subcellular localization of αA- and αB-crystallins were further analyzed in vivo and in a retinal neuronal cell model using immunoprecipitation and fractionation METHODS:Survival of retinal neurons to metabolic stress after overexpression and knock-down of α-crystallins was used to measure their neuroprotective properties. RESULTS:All 10 of the crystallins identified in retinal lysates from both models of type 1 diabetes were strongly upregulated, coinciding with increased retinal cell death and expression of proapoptotic proteins Bax and Bcl-Xs. Diabetes strongly reduces the chaperone function of α-crystallins by reducing their solubility and disrupting the normal interaction of α-crystallins with Bax. The same properties disrupted by diabetes were confirmed to be critical for the neuroprotective effect of the overexpression of α-crystallins in retinal neurons in culture. CONCLUSIONS:Both chemically and genetically induced diabetic models are characterized by upregulation of α-, β-, and γ-crystallins in the retina. Despite being overexpressed, the molecular properties of α-crystallins are disrupted by diabetes and contribute to the loss of neuroprotective function. Identification and prevention of these alterations could lead to the emergence of new therapies for diabetic retinopathy.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Losiewicz MK,Fort PEdoi
10.1167/iovs.10-6931subject
Has Abstractpub_date
2011-08-24 00:00:00pages
5034-42issue
9eissn
0146-0404issn
1552-5783pii
iovs.10-6931journal_volume
52pub_type
杂志文章abstract：PURPOSE:To determine the impact of repetitive nonlethal oxidant injury with hydroquinone (HQ) on regulation of cell membrane blebbing and molecules, which are essential in extracellular matrix turnover (ECM) maintenance, especially matrix metalloproteinase (MMP)-2, tissue inhibitor of MMP (TIMP)-2, and type IV collagen...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.05-1230
更新日期：2006-09-01 00:00:00
abstract：PURPOSE:Fundus autofluorescence (FAF), as an index of lipofuscin accumulation in the retinal pigment epithelium (RPE), provides indirect information on the level of metabolic activity of the RPE and thus the integrity of the RPE/photoreceptor complex. To investigate whether the photoreceptor/RPE complex is still viable...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.03-1208
更新日期：2004-08-01 00:00:00
abstract：PURPOSE:It is known that the pattern electroretinogram (PERG) of normal subjects is reduced temporarily after short-term elevation of intraocular pressure (IOP). The authors evaluated PERG changes in ocular hypertension during and after transient IOP elevation. METHODS:Steady state (8 Hz) PERGs to sinusoidal gratings ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：PURPOSE:The aim of this study was to evaluate the changes in tumor burden and hypoxia in the LH(BETA)T(AG) retinal tumors after treatment with a focal, single-modality, and combination therapy using periocular carboplatin and 2-deoxy-d-glucose (2-DG). METHODS:Seventeen-week-old LH(BETA)T(AG) transgenic mice (n = 25) w...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.09-5033
更新日期：2010-12-01 00:00:00
abstract：PURPOSE:Elevated intraocular pressure (IOP), sensed as mechanical stretching by trabecular meshwork (TM) cells, triggers extracellular matrix (ECM) remodeling. In addition to changes in gene expression, alternative mRNA splicing may alter ECM protein isoforms. Changes in mRNA expression and alternative splicing of four...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.06-0875
更新日期：2007-03-01 00:00:00
abstract：PURPOSE:The prevalence of cataract increases with age. Conversely, the abundance of native α-crystallin diminishes with age and cataract development. We hypothesize replenishing lens α-crystallin may delay or prevent cataract. Herein we investigated the ability of cell penetration peptides (CPP) to enhance entry of α-c...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.12-10947
更新日期：2013-01-02 00:00:00
abstract：PURPOSE:In corneal endothelial cells, intercellular Ca(2+) waves elicited by a mechanical stimulus involve paracrine intercellular communication, mediated by ATP release via connexin hemichannels, as well as gap junctional intercellular communication. Both mechanisms are inhibited by thrombin, which activates RhoA and ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.06-1062
更新日期：2007-04-01 00:00:00
abstract：PURPOSE:To evaluate and compare the use of the Kowa laser flare cell meter and intravenous anterior chamber fluorophotometry in assessment of the blood-aqueous barrier after cataract surgery. METHOD:Laser flare and cell measurements and fluorophotometry were performed at 1 and 3 months after surgery in 48 eyes of 44 p...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1993-10-01 00:00:00
abstract：PURPOSE:Hyperreflective foci (HFs) are observable within the neurosensory retina in diabetic macular edema (DME) using spectral domain optical coherence tomography (SD-OCT). HFs have also been seen in wet age-related macular degeneration (AMD), although the origin is still unknown; however, they reduced significantly d...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.12-9950
更新日期：2012-08-24 00:00:00
abstract：:The existence of wide-band, phase-specific channels in the human visual system has been suggested in recent investigations. We used a number of adapting gratings to test for phase-specific adaptation effects. Observers were asked to discriminate between a simple 3 cpd sine-wave grating, (3), and a complex grating comp...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1978-05-01 00:00:00
abstract：PURPOSE:To investigate the dynamic effect of tear lipocalins (TLs), the major lipid-binding protein in tears, at aqueous-cornea and lipid-aqueous interfaces, and their potential contribution to surface tension in the tear film. METHODS:Human apo- and holo-TLs were applied to the aqueous subphase in a Langmuir trough, ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1999-12-01 00:00:00
abstract：:We examined the sources of artifacts of vitreous fluorophotometry (VF), a technique used to assess the permeability of the blood-retinal barrier. By performing in vitro measurements in a model eye and in vivo readings in humans, we investigated the influence of various concentrations of fluorescein in the anterior cha...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1982-05-01 00:00:00
abstract：PURPOSE:To study the spatial distribution of posterior pole choroidal thickness (CT) in healthy eyes using spectral domain optical coherence tomography (SD-OCT). METHODS:Fifty-nine eyes from 30 subjects with no retinal or choroidal disease were examined with high-definition (HD) OCT using macular volume cube scanning ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.11-8046
更新日期：2011-09-01 00:00:00
abstract：PURPOSE:To determine whether the size and configuration of the optic chiasm in humans with albinism is different from that in normal control subjects. METHODS:Seventeen patients and 15 control subjects underwent magnetic resonance imaging of the entire head. Images were reformatted to the chiasm region and analyzed wi...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.02-0156
更新日期：2003-01-01 00:00:00
abstract：PURPOSE:To investigate the use of topically applied FK506, a new immunosuppressive compound, systemic and ocular absorption was determined in serum and various ocular tissues. METHODS:Two drops of 20 microliters FK506 were applied using oil dissolved (OD-FK506) or liposome-bound (LIP-FK506) drug. FK506 concentrations ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1993-08-01 00:00:00
abstract：PURPOSE:To evaluate a porcine anterior chamber perfusion model and to test the transferability of data obtained with this model to the human system. METHODS:Porcine eyes were obtained from a local abattoir and processed within 2 hours after death. Anterior chambers of 42 pairs of eyes were dissected with removal of le...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.05-1393
更新日期：2006-05-01 00:00:00
abstract：PURPOSE:To determine the effects of blocking substance P (SP) interactions with its major receptor (NK1-R) using the antagonist spantide I in susceptible mice infected with Pseudomonas aeruginosa. METHODS:Immunohistochemistry and enzyme immunosorbent assay (EIA) tested levels of SP in the cornea of B6 and BALB/c mice....
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.06-0882
更新日期：2007-02-01 00:00:00
abstract：PURPOSE:Excitotoxicity has been proposed to play a pivotal role in retinal damage, but the mechanisms that underlie retinal damage are not clearly understood. In this study, the role of matrix metalloproteinases in excitotoxin-mediated retinal damage was investigated. METHODS:KA, CNQX (6-cyano-7-nitroquinoxaline-2,3,-...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.03-1239
更新日期：2004-07-01 00:00:00
abstract：PURPOSE:To evaluate symptoms, signs, and the levels of 16 tears inflammatory mediators of dry eye (DE) patients exposed to an environment simulating an in-flight air cabin in an environmental chamber. METHODS:Twenty DE patients were exposed to controlled environment simulating an in-flight airplane cabin (simulated in...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.12-11361
更新日期：2013-03-01 00:00:00
abstract：PURPOSE:Migration of Müller glial cells is enhanced in proliferative retinopathies, but the mechanisms involved are ill defined. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid synthesized by sphingosine kinase (SphK), which promotes proliferation, migration, and inflammation, acting as an intracellular media...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.14-16195
更新日期：2015-09-01 00:00:00
abstract：PURPOSE:To determine whether blur adaptation influences blur sensitivity and blur discrimination thresholds in young adult myopes and emmetropes. In addition, to determine whether there is a differential effect of blur adaptation on blur sensitivity and discrimination between refractive error groups. METHODS:Proximal ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.06-0836
更新日期：2007-06-01 00:00:00
abstract：:Herpes simplex virus type 1 (HSV-1) inoculated directly into the anterior chamber of the mouse eye induced an acute inflammatory process in both the injected eye and its uninjected (contralateral) counterpart. In the former, a rapid intense inflammatory reaction developed in the anterior segment (cornea, anterior cham...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1984-09-01 00:00:00
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
doi：10.1167/iovs.15-18559
更新日期：2016-02-01 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
abstract：PURPOSE:To characterize the thickness profile of the corneal epithelium and the Bowman's layer across the horizontal meridian. METHODS:Forty-four eyes of 22 healthy subjects were investigated in this study. Ultra-high resolution anterior segment spectral domain-optical coherence tomography (SD-OCT) was used to assess ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.09-4748
更新日期：2011-06-01 00:00:00
abstract：PURPOSE:The influence of genetic and prenatal environmental factors on characteristics of saccadic performance were evaluated in young monozygotic (MZ) twins (8-19 years old) of known chorion type. METHODS:Saccadic eye movements were recorded using an infrared system. Saccadic latency, accuracy, and parameters of ampl...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1998-10-01 00:00:00
abstract：PURPOSE:To test whether retinal pigment epithelial (RPE) cells are able to induce myeloid-derived suppressor cell (MDSC) differentiation from bone marrow (BM) progenitors. METHODS:BM cells were cocultured with or without RPE cells in the presence of GM-CSF and IL-4. Numbers of resultant MDSCs were assessed by flow cyt...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.11-8377
更新日期：2012-02-23 00:00:00
abstract：Purpose:Ocular neovascularization (NV) is a pathologic process characterized by the proliferation and infiltration of various types of cells such as RPE, glial, and endothelial cells, which interact with proangiogenic factors and inflammatory cytokines. Endocan is known to be enriched in retinal endothelial tip cells u...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.17-22945
更新日期：2018-02-01 00:00:00
abstract：PURPOSE:Since, to our knowledge, there are no reports on the prevalence of the blaNDM-1 gene among ocular isolates of Enterobacteriaceae, and only limited information on the prevalence of extended spectrum beta-lactamases (ESBLs) among ocular bacterial isolates are available, our study was undertaken. METHODS:A prospe...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.12-10467
更新日期：2012-08-07 00:00:00
abstract：PURPOSE:Persistent hyperplastic primary vitreous (PHPV) is an idiopathic developmental eye disease associated with failed involution of the hyaloid vasculature. The present work addressed the pathogenesis of PHPV in a mouse model that replicates many aspects of the human disease. METHODS:Ophthalmoscopic and histologic...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.04-0349
更新日期：2004-10-01 00:00:00
