Abstract:
:Post-translational modifications by transglutaminase may contribute to the remodeling of cellular architecture in the development of lens fiber cells, and there is evidence that the enzyme may also play a role in cataract formation. It catalyses hydrolytic deamidations as well as amide exchanges on select glutamine side chains at endo positions in a small subset of proteins of the lens. N epsilon(gamma-glutamyl)lysine crosslinks, the characteristic hallmarks of transglutaminase activity, were identified in polymers isolated from human cataract. Following up on our earlier studies relating to the inhibition of protein crosslinking by the Ca(2+)-activated transglutaminase in the lens, we have now examined the effects of 2-[(2-oxopropyl)thio]-imidazolium derivatives, recently described as active site-directed inhibitors for this family of enzymes. First, we have shown that the compounds at concentrations of 1-2 microM were effective in blocking the transamidating activities of partially purified lens transglutaminase. Then we focused on their efficacy in preventing the formation of the ca. 55 kDa beta crystallin dimers in the whole lens tissue. The production of these dimers, crosslinked by N epsilon(gamma-glutamyl)lysine isopeptide bridges, is an early sign of transglutaminase action in rabbit lens, and it can be readily documented by the SDS-PAGE analysis of proteins remaining in the soluble phase after brief exposure of the homogenate to Ca2+. The new compounds proved to be potent inhibitors of transglutaminase also in this preparation, preventing the crosslinking event at ca. 1 microM concentration. Moreover, even when applied at a 1,000-fold greater concentration (2 mM), they did not interfere with the action of calpain which, similarly to the activation of the transglutaminase system, is triggered by the addition of Ca2+. The high selectivity of the new compounds for differentially blocking only the transglutaminase and not the calpain of the lens, is all the more remarkable because these two enzymes share several mechanistic and structural similarities.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
Lorand L,Stern AM,Velasco PTdoi
10.1006/exer.1997.0463subject
Has Abstractpub_date
1998-05-01 00:00:00pages
531-6issue
5eissn
0014-4835issn
1096-0007pii
S0014-4835(97)90463-2journal_volume
66pub_type
杂志文章abstract:BACKGROUND:Indirect traumatic optic neuropathy (ITON) is a major cause of permanent loss of vision after blunt head trauma. Neuroinflammation plays a crucial role in neurodegenerative diseases. The present study concentrated on JNK/c-Jun-driven NLRP3 inflammasome activation in microglia during the degeneration of retin...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2020.108335
更新日期:2021-01-01 00:00:00
abstract::The purpose of this study was to determine whether trans-scleral pressure affects scleral solute permeability by altering scleral thickness or hydration, and to investigate the sustained release delivery of dexamethasone. Scleral sections from donor human globes were mounted for in vitro flux studies. Scleral thicknes...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/s0014-4835(03)00211-2
更新日期:2004-03-01 00:00:00
abstract::The transmembrane glycoprotein CD44 is a cell adhesion molecule which has recently been localized in a variety of cell types. It mediates cell attachment to extracellular matrix components and also binds to the actin cytoskeleton within the cell. In this study, the presence and distribution of CD44 in the mouse retina...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1006/exer.1994.1026
更新日期:1994-03-01 00:00:00
abstract::Fiber cells of the ocular lens are arranged in a series of concentric shells. New growth shells are added continuously to the lens surface and, as a consequence, the preexisting shells are buried. To focus light, the refractive index of the lens cytoplasm must exceed that of the surrounding aqueous and vitreous humors...
journal_title:Experimental eye research
pub_type: 杂志文章,评审
doi:10.1016/j.exer.2016.03.009
更新日期:2017-03-01 00:00:00
abstract::The causes of vitreous humor (VH) liquefaction remain unclear. Diabetes accelerates this process and other ocular diseases. The weakening of the blood-retina barrier observed with diabetes could enhance the rate of transfer of relatively small molecules such as glucose (Glu) and phospholipids (PLs) from the retina to ...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2020.108221
更新日期:2020-11-01 00:00:00
abstract::Endocannabinoid system involves in neuroprotective effects on the central neural system. The cannabinoid receptor 1 (CB1R) is widely expressed in the mouse retina. However, the role of cannabinoid receptors in the retina remains unclear. In this work, we established a photoreceptor degeneration mouse model via N-methy...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2017.11.001
更新日期:2018-02-01 00:00:00
abstract::We examine the immunoreactivity of the non-receptor tyrosine kinase, c-Src kinase and its downstream molecule, signal transducer and activator of transcription 3 (pStat3) in retinoblastoma (RB), and correlation with invasiveness and differentiation. Tumor samples from 40 patients with RB were available for the study. ...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2006.02.011
更新日期:2006-10-01 00:00:00
abstract::In a previous investigation into the fate of fluorescently labelled antigen (Ag) injected into the anterior chamber (AC) of the rat eye, a large number of Ag+ cells were noted in the conventional and non-conventional aqueous humour outflow pathways together with the external limbus. The aim of this study was to invest...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2004.06.009
更新日期:2004-10-01 00:00:00
abstract::A simple culture method that was recently developed in our laboratory was applied to the chick iris tissues to characterize neural stem/progenitor-like cells. Iris tissue is a non-neuronal tissue and does not contain any neuronal cells. In the present study we isolated iris tissues from chick embryos just prior to hat...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2014.04.007
更新日期:2014-06-01 00:00:00
abstract::Specific [3H]-dexamethasone binding sites were demonstrated in bovine corneal cytosol using titration analyses. Specific glucocorticoid binding to corneal cytosol exhibited a single class of sites with apparent dissociation constants of 4-6 nM and 68-72 fmol binding sites mg-1 cytosolic protein. Association of steroid...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/0014-4835(84)90188-x
更新日期:1984-04-01 00:00:00
abstract::Evidence is presented that alpha-crystallin isolated at 37 degrees C exists as a species, alpha m, which has a minimum molecular weight of about 320000 and a sedimentation coefficient of about 12 S. The amino acid composition, subunit distribution, near- and far-UV CD spectra and immunochemical properties were identic...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/0014-4835(83)90173-2
更新日期:1983-10-01 00:00:00
abstract::Choroidal neovascularization (CNV) associated with the 'wet' form of age related macular degeneration (AMD) is one of the most common causes of central vision loss among the elderly. The 'wet' form of AMD is currently treated by intravitreal delivery of anti-VEGF agents. However, intravitreal injections are associated...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2015.09.005
更新日期:2015-11-01 00:00:00
abstract::Previous studies in the laboratory have shown that platelet-activating factor (PAF), a potent inflammatory mediator that accumulates rapidly in the cornea after an injury, stimulates the expression of urokinase (uPA) and matrix metalloproteinase-1 (MMP-1) and -9 (MMP-9). Tissue inhibitors of MMPs (TIMPs) and plasminog...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1006/exer.2001.1135
更新日期:2002-03-01 00:00:00
abstract::Fungal keratitis is a common disease that causes blindness. An effective animal model for fungal keratitis is essential for advancing research on this disease. Our objective is to develop a novel mouse model of Fusarium solani keratitis through the inoculation of fluorescent-labeled fungi into the cornea to facilitate...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2013.03.002
更新日期:2013-05-01 00:00:00
abstract::Adipose-Derived Stem Cells (ADSCs) have an important contribution in regenerative medicine ranging from testing stem cell therapy for disease treatment in pre-clinical models to clinical trials. For immediate use of stem cells for therapy, there is a requirement of the high dose of stem cells at different time points ...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2019.107860
更新日期:2019-12-01 00:00:00
abstract::Pericytes exert an important influence on the control of retinal blood flow; however, little is known regarding the molecular basis of retinal pericyte excitability. The purpose of this study was to elucidate the signaling pathway of how prostacyclin (PGI2), an important endogenous regulator of retinal blood flow, sti...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2006.07.011
更新日期:2006-12-01 00:00:00
abstract::Sodium hyaluronates with molecular weights of 18000, 500000 and 4 x 10(6), labelled with either 3H or 14C, were injected into the anterior chamber or into the centre of the vitreous body of rabbits and their rates of disappearance were followed. The out-flow from the anterior chamber in anaesthetized animals was virtu...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/0014-4835(83)90043-x
更新日期:1983-04-01 00:00:00
abstract::The corneal endothelial monolayer helps maintain corneal transparency through its barrier and ionic "pump" functions. This transparency function can become compromised, resulting in a critical loss in endothelial cell density (ECD), corneal edema, bullous keratopathy, and loss of visual acuity. Although penetrating ke...
journal_title:Experimental eye research
pub_type: 杂志文章,评审
doi:10.1016/j.exer.2011.08.014
更新日期:2012-02-01 00:00:00
abstract::Myofibroblasts expressing α-smooth muscle actin (α-SMA) are the key cellular mediator of fibrosis. Fibrovascular epiretinal membranes from patients with proliferative diabetic retinopathy (PDR) are characterized by the accumulation of a large number of myofibroblasts. We explored the hypothesis that proliferating endo...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2015.01.023
更新日期:2015-03-01 00:00:00
abstract::The effect of a 'soft' anti-inflammatory corticosteroid on the corneal wound healing was investigated in rabbits. Albino rabbits were treated with soft steroid and dexamethasone after linear perforating corneal incision. Soft drug design is aimed to control and direct the drug activity and in vivo metabolism to nontox...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/0014-4835(90)90229-n
更新日期:1990-02-01 00:00:00
abstract::Ciliary ganglionectomy inhibits the development of myopia in chicks (Schmid et al., 1999), but has no effect on the compensatory responses to spectacle lenses (Schmid and Wildsoet, 1996). This study was done to assess the potential influence of the other parasympathetic input to the choroid, the pterygopalatine gangli...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2012.07.002
更新日期:2012-09-01 00:00:00
abstract::Purified retinal pigment epithelial cells of bovine eyes have been fractionated by a series of buffer and detergent extractions. The electropherogram of the buffer-insoluble, Triton X-100-soluble fraction (RPE-TS) exhibits a major polypeptide band of M(r) 65 kDa and a variety of minor components. Electrophoretically p...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/0014-4835(92)90008-g
更新日期:1992-12-01 00:00:00
abstract::Previous studies have shown that corneal endothelial cells contain mRNA and protein of various growth factors. However, the role of these endogenous growth factors in corneal endothelial wound healing is not fully elucidated. In the present study, we investigated the role of endogenous factors and several growth facto...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1006/exer.2000.0918
更新日期:2000-12-01 00:00:00
abstract::An experimental study was conducted on eight litters of newborn rats to evaluate the effects of supplemental oxygen administration on the retinal vasculature. The animals and their mothers were kept inside a pressure chamber and treated for the first 5 days of life. On the sixth day, they were removed and kept for fiv...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/s0014-4835(87)80179-3
更新日期:1987-03-01 00:00:00
abstract::Harmonic analysis was used to characterize the rabbit flicker ERG elicited by sinusoidally modulated full-field stimuli under light-adapted conditions. The frequency-response function for fundamental amplitude, derived from Fourier analysis of the ERG waveforms, exhibited two limbs, with an amplitude minimum at approx...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2010.10.005
更新日期:2010-12-01 00:00:00
abstract::Structure and function of the retina mainly rely on its fatty acid (FA) composition. Evidence from epidemiological studies and from animal experiments indicates that FA composition of the retina is influenced by the diet. Mice under chronic high-fat diet (HFD) develop metabolic syndrome, a risk factor for diabetes tha...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2020.108059
更新日期:2020-07-01 00:00:00
abstract::The routine cultivation of human corneal endothelial cells, with the view to treating patients with endothelial dysfunction, remains a challenging task. While progress in this field has been buoyed by the proposed existence of progenitor cells for the corneal endothelium at the corneal limbus, strategies for exploitin...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2014.07.002
更新日期:2014-10-01 00:00:00
abstract::Lacritin is a mitogen of human salivary gland cells as well as a stimulator of human corneal epithelial cells. It is expected to be an important factor in maintaining the surrounding ocular surface. The monkey would be a relevant animal model in which to study the role of lacritin in ophthalmic physiology and patholog...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2007.07.019
更新日期:2007-11-01 00:00:00
abstract::This lecture summarizes studies on the effects of some of the neuropeptides which seem to be present in somatosensory and autonomic nerves in the uvea. Release of these peptides is likely to explain nerve induced effects in the eye which are not due to classical transmitters. Trigeminal nerve fibres in the eye seem to...
journal_title:Experimental eye research
pub_type: 杂志文章,评审
doi:10.1016/0014-4835(91)90138-5
更新日期:1991-07-01 00:00:00
abstract::Oxidative stress and inflammation are important pathological mechanisms in many neurodegenerative diseases, including age-related macular degeneration (AMD). The very low-density lipoprotein receptor knockout mouse (Vldlr-/-) has been identified as a model for AMD and in particular for retinal angiomatous proliferatio...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2013.08.003
更新日期:2013-11-01 00:00:00