Abstract：
:Between 5 and 70% of genetic disease is caused by in-frame nonsense mutations, which introduce a premature termination codon (PTC) within the disease-causing gene. Consequently, during translation, non-functional or gain-of-function truncated proteins of pathological significance, are formed. Approximately 50% of all inherited retinal disorders have been associated with PTCs, highlighting the importance of novel pharmacological or gene correction therapies in ocular disease. Pharmacological nonsense suppression of PTCs could delineate a therapeutic strategy that treats the mutation in a gene- and disease-independent manner. This approach aims to suppress the fidelity of the ribosome during protein synthesis so that a near-cognate aminoacyl-tRNA, which shares two of the three nucleotides of the PTC, can be inserted into the peptide chain, allowing translation to continue, and a full-length functional protein to be produced. Here we discuss the mechanisms and evidence of nonsense suppression agents, including the small molecule drug ataluren (or PTC124) and next generation 'designer' aminoglycosides, for the treatment of genetic eye disease.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
Richardson R,Smart M,Tracey-White D,Webster AR,Moosajee Mdoi
10.1016/j.exer.2017.01.001subject
Has Abstractpub_date
2017-02-01 00:00:00pages
24-37eissn
0014-4835issn
1096-0007pii
S0014-4835(17)30007-6journal_volume
155pub_type
杂志文章,评审abstract：:Argon laser energy was applied to the trabecular meshwork of pigmented rabbits in an attempt to develop an animal model of 'glaucoma'. Laser energy was varied to determine the optimal level needed to produce sustained ocular hypertension. An initial response of ocular hypertension followed by hypotension was observed ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(86)90067-9
更新日期：1986-12-01 00:00:00
abstract：:Optic fissure closure defects result in uveal coloboma, a potentially blinding condition affecting between 0.5 and 2.6 per 10,000 births that may cause up to 10% of childhood blindness. Uveal coloboma is on a phenotypic continuum with microphthalmia (small eye) and anophthalmia (primordial/no ocular tissue), the so-ca...
journal_title：Experimental eye research
pub_type： 杂志文章,评审
doi：10.1016/j.exer.2020.107940
更新日期：2020-04-01 00:00:00
abstract：:The purpose of this study was to evaluate the composition of ghost vessels and the newly identified intravitreal structures type 1 and 2 (IVS-1 and 2) observed in the rabbit vitreous body. Rabbit eyes (n = 10, 0.5- approximately 36 months of age) were fixed and embedded in plastic. Post-embedding immuno transmission e...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.2000.0865
更新日期：2000-08-01 00:00:00
abstract：:A long-term culture of choriocapillary endothelial cells (CCE) from bovine eyes has been established. We developed a micromanipulative technique with a dissecting microscope for isolation of choriocapillary sheets after a prolonged trypsinization of choroid tissues. We then used a cell sweeping technique to ensure a c...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1993.1096
更新日期：1993-07-01 00:00:00
abstract：:Owing to a rapidly aging population, vision impairment caused by age-related cataract has become very common. Age-related cataract has also become one of the principal causes of blindness, and apoptosis of lens epithelial cells contributes to non-congenital cataract development. Previous studies have reported that mic...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2016.04.018
更新日期：2016-06-01 00:00:00
abstract：:Deficient cGMP-phosphodiesterase (cGMP-PDE) activity results in elevated levels of cGMP in the rd retina before any pathological signs are observed. Since the enzyme is present in rd retina, although it is barely activated by light, we determined whether its synthesis starts at the same time as that of cGMP-PDE in nor...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(88)80026-5
更新日期：1988-03-01 00:00:00
abstract：:microPx-11, a ferriheme undecapeptide proteolytic degradation product of cytochrome C is shown to be a peroxidase with broad specificity degrading H2O2 and tertiary butyl hydroperoxide. It is also capable of effectively eliminating superoxide and hydroxyl radical. The peroxidase loses activity in the presence of perox...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1997.0336
更新日期：1997-10-01 00:00:00
abstract：:A single intraperitoneal dose of endotoxin (lipopolysaccharide or LPS) induces an acute inflammatory response in the uveal tract of rats. This inflammation is characterized by a breakdown of the blood/aqueous barrier within 3 hr after the LPS and the subsequent development of clinical disease and a cellular infiltrate...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(84)90065-4
更新日期：1984-11-01 00:00:00
abstract：:The goal of this study was to investigate the efflux of K(+) from human corneal limbal epithelial cells (HCLE) exposed to ambient levels of UVB, which is known to cause apoptosis, and to examine the effect of K(+) channel blockers on loss of potassium induced by UVB. HCLE cells were exposed to 100-200 mJ/cm(2) UVB, fo...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2011.02.019
更新日期：2011-05-01 00:00:00
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journal_title：Experimental eye research
pub_type： 杂志文章,评审
doi：10.1016/j.exer.2004.06.011
更新日期：2004-09-01 00:00:00
abstract：:Neovascular eye diseases such as wet age-related macular degeneration and proliferative diabetic retinopathy are two of the most common causes of irreversible visual loss. Although mediated by vascular endothelial growth factor (VEGF), the mechanisms of these diseases are not fully understood. Molecular inhibitors of ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2011.09.010
更新日期：2011-11-01 00:00:00
abstract：:We studied the early protein profile in the ocular tissue extracted after LASIK and SMILE surgery. SMILE and LASIK was performed in contralateral eyes and stromal tissue samples were collected from 10 eyes of 5 donors. The stromal tissue samples were analyzed using label free quantification approach and ITRAQ labellin...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2020.107936
更新日期：2020-03-01 00:00:00
abstract：:The binding of eight fluorescence-labeled lectins to the photoreceptors of the monkey retina was investigated using a post-embedding staining method. Concanavalin A (specific for mannosyl and glucosyl residues) bound to the outer and inner segments of both rods and cones, while the degree of staining was more intense ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(83)90094-5
更新日期：1983-01-01 00:00:00
abstract：:Reactive nitrogen species, in particular, peroxynitrite (ONOO(-)) have been proposed to play an important role in the pathogenesis of endotoxin-induced uveitis (EIU). Tyrosine nitration by ONOO(-) has been shown in other model systems to inhibit the activity of the superoxide anion quenching enyzme, manganese superoxi...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.2002.1141
更新日期：2002-04-01 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：:This review is focused on iron metabolism in the retina and in the lens and its relation to their respective age-related pathologies, macular degeneration (AMD) and cataract (ARC). Several aspects of iron homeostasis are considered first in the retina and second in the lens, paying particular attention to the transpor...
journal_title：Experimental eye research
pub_type： 杂志文章,评审
doi：10.1016/j.exer.2010.03.003
更新日期：2010-06-01 00:00:00
abstract：:The hyaluronan content during wound healing following excimer laser photoablation was investigated. Rabbit corneas were photoablated (Summit Omnimed, 193 nm, 5 mm diameter, 50 microns and 100 microns depth). Central optical zones of photoablated and contralateral corneas were removed 7, 30 and 90 days after surgery. C...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1996.0212
更新日期：1997-03-01 00:00:00
abstract：:Proliferative diabetic retinopathy (PDR) is characterized by intraocular formation of fibroglial vascularized tissue by active vasoproliferative mechanisms. Using immunocytochemistry, we have studied changes in the distribution pattern of fibronectin (FN), laminin (LN), vitronectin (VN) and their receptors in the newl...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(05)80079-x
更新日期：1995-01-01 00:00:00
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journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2019.107755
更新日期：2019-10-01 00:00:00
abstract：:Human retinal pigmented epithelial (RPE) cells cultured on plastic, unlike RPE in situ, often fail to density arrest, do not produce melanin, and do not express mRNA for cellular retinaldehyde binding protein (CRALBP). When human RPE are cultured on the extracellular matrix produced by bovine corneal endothelial cells...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1993.1158
更新日期：1993-11-01 00:00:00
abstract：:The purpose of this study was to investigate the expression of the EGF family of growth factors and EGF receptor subtypes (ErbB1-4) present in lacrimal gland and determine the effects of these growth factors on different functions of rat lacrimal gland. RT-PCR was used to detect mRNA expression in the lacrimal gland o...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2004.10.006
更新日期：2005-03-01 00:00:00
abstract：:Our previous gene expression analysis suggested that conjunctival epithelial cells of Sjögren's syndrome (SS) are inclined to hyper-proliferation and keratinisation status. The goal of this study is to elucidate whether such pathological situations really exist in the conjunctival epithelium of SS. Also, involvement o...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2005.07.009
更新日期：2006-03-01 00:00:00
abstract：:The purpose of the study was to determine histologic findings after successful laser trabeculoplasty in eyes with glaucoma. Previous studies have examined eyes in which laser did not lower intraocular pressure, or examined only the region of the laser burn itself. Nineteen autopsy eyes from 14 donors with either prima...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2007.07.009
更新日期：2007-10-01 00:00:00
abstract：PURPOSE:To characterize multilamellar bodies (MLBs), determine their distribution along the optic axis and predict their potential Mie scattering within human age-related nuclear cataracts. Previous studies restricted to the equatorial plane have shown that MLBs are rare spherical objects that are 1-4 microm in diamete...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2004.05.017
更新日期：2004-10-01 00:00:00
abstract：:Various concentrations of three dopamine antagonists (fluphenazine, haloperidol and sulpiride) with different affinities to the receptor subtypes were applied in order to test their effect on responses from outer (isolated PIII-component of the ERG), middle (b-wave) and inner (optic nerve response, ONR) retinal layers...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(91)90038-g
更新日期：1991-04-01 00:00:00
abstract：:We have used a polyclonal antiserum to bovine ciliary epithelium, a secretory tissue involved in the formation of aqueous humor, to immunoscreen a directional lambda gt11 Sfi-Not cDNA expression library prepared from bovine ciliary epithelium poly(A)+ RNA. After immunoscreening 6 x 10(5) independent clones, 41 cDNA cl...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(92)90175-r
更新日期：1992-11-01 00:00:00
abstract：:As a potential drug for the prevention of secondary cataract formation (SCF), we investigated the effect of Aclacinomycin A (ACM) on the growth of cultures of porcine lens epithelial cells in vitro. ACM is an anthracycline that has been used in the treatment of acute myeloid leukemia in the human for many years. It ha...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：
更新日期：1998-01-01 00:00:00
abstract：:Transforming growth factor β (TGFβ) signaling is one of the most important signaling pathways regulating cell behavior in ocular tissues. Its functions are mainly linked to tissue fibrosis and inflammatory responses in ophthalmology. In epithelial cells, however, the growth inhibitory activity of TGFβ was reported in ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2019.03.014
更新日期：2019-05-01 00:00:00
abstract：:Previous studies suggest that an alpha 2-related isoform of the catalytic subunit is predominant in the lens fiber cells. The alpha 1 isoform is predominant in the lens epithelium (Garner, Horwitz and Enomoto, 1992). Data are presented to show that strophanthidin-sensitive K+ transport is sustained by both of these le...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1994.1068
更新日期：1994-06-01 00:00:00
abstract：:Intraocular pressure (IOP) is an important risk factor for glaucoma, and the response of the ONH and surrounding tissues to elevated IOP are often investigated to better understand pathophysiology. In vivo structure including that of the optic nerve head (ONH) and surrounding tissue of the eye are often assessed using...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2018.01.025
更新日期：2018-04-01 00:00:00
