Abstract：
:There is currently no available method to efficiently deliver proteins across the plasma membrane of photoreceptor or retinal pigment epithelium (RPE) cells in vivo. Thus, current clinical application of recombinant proteins in ophthalmology is limited to the use of proteins that perform their biological function extracellularly. The ability to traverse biological membranes would enable the mobilization of a significantly larger number of proteins with previously well characterized properties. Nucleolin is abundantly present on the surface of rapidly dividing cells including cancer cells. Surprisingly, nucleolin is also present on the surface of photoreceptor cell bodies. Here we investigated whether nucleolin can be utilized as a gateway for the delivery of proteins into retinal cells following intravitreal injection. AS1411 is a G-quartet aptamer capable of targeting nucleolin. Subsequent to intravitreal injection, fluorescently labeled AS1411 localized to various retinal cell types including the photoreceptors and RPE. AS1411 linked to streptavidin (a ∼50 kDa protein) via a biotin bridge enabled the uptake of Streptavidin into photoreceptors and RPE. AS1411-Streptavidin conjugate applied topically to the cornea allowed for uptake of the conjugate into the nucleus and cytoplasm of corneal endothelial cells. Clinical relevance of AS1411 as a delivery vehicle was strongly indicated by demonstration of the presence of cell surface nucleolin on the photoreceptors, inner neurons and ganglion cells of human retina. These data support exploration of AS1411 as a means of delivering therapeutic proteins to diseased retina.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
Leaderer D,Cashman SM,Kumar-Singh Rdoi
10.1016/j.exer.2016.02.009subject
Has Abstractpub_date
2016-04-01 00:00:00pages
380-392eissn
0014-4835issn
1096-0007pii
S0014-4835(16)30026-4journal_volume
145pub_type
杂志文章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：:Cynomolgus (Macaca fascicularis) monkeys from three families, which showed symptoms of early onset macular degeneration was studied. Two proteins, albumin and glyceraldehyde 3-phosphate dehydrogenase, were found to have markedly altered concentrations in whole retina of the monkeys with early onset macular degeneratio...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1996.0026
更新日期：1996-03-01 00:00:00
abstract：:Dexamethasone is a glucocorticoid that is widely used in the ophthalmic arena. The recent FDA approved dexamethasone implant can provide a three month efficacy but with high rate of drug related cataract and high intraocular pressure (IOP). It seems that higher steroid in aqueous humor and around lens may be associate...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2014.11.002
更新日期：2014-12-01 00:00:00
abstract：:Nitric oxide (NO) production by vascular endothelium is important in regulation of blood flow. Reduced production of NO can adversely affect blood flow and other vascular functions. We investigated the expression of three nitric oxide synthase (NOS) isoforms in retina and choroid of aged human eyes and eyes with AMD. ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2009.10.004
更新日期：2010-01-01 00:00:00
abstract：:Purpose of the study was to develop and assess a novel controlled drug delivery system of latanoprost acid (LA). Poly(lactide)/Monomethoxy-poly(ethyleneglycol) (PLA-PEG) nanoparticles (NPs) were prepared using an emulsification-solvent evaporation technique. NPs were characterized in vitro according to their size, ζ-p...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2013.04.007
更新日期：2013-07-01 00:00:00
abstract：:Small heat shock proteins and alpha-crystallins are related proteins with several common structural and functional properties including homologous amino acid sequences and similar chaperone-like activity. Furthermore, small heat shock proteins and alpha-crystallins are phosphorylated in vivo at serine residues within ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1997.0324
更新日期：1997-08-01 00:00:00
abstract：:The aim of the study was to investigate the molecular genetics of uveal melanoma (UM) metastases and correlate it with disease progression. Twelve pathologically confirmed UM metastases from 11 patients were included. Molecular genetic alterations in chromosomes 3 (including the BAP1 region), 8q, 6p, and 1p were inves...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2012.04.010
更新日期：2012-07-01 00:00:00
abstract：:Rifampicin, an antibacterial drug widely used in the treatment of tuberculosis and leprosy, has recently been reported to have anti-oxidative and anti-apoptotic effects. However, its anti-angiogenic effect has not been investigated. We examined its anti-angiogenic effect on tube formation and proliferation by human um...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2007.10.003
更新日期：2008-01-01 00:00:00
abstract：:Misregulation of the innate immune response and other immune-related processes have been suggested to play a critical role in the pathogenesis of a number of different neurodegenerative diseases, including age related macular degeneration. In an animal model for photoreceptor degeneration, several genes of the innate ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2006.08.017
更新日期：2007-01-01 00:00:00
abstract：:Hyaluronan (HA) distribution in the posterior eye wall from the vitreous through the sclera, with special consideration to localization in the retina and interphotoreceptor matrix (IPM), was evaluated in human, bovine, guinea pig, dog, rat and mouse tissues using a specific probe for HA (bHABC, biotinylated hyaluronan...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1997.0422
更新日期：1998-02-01 00:00:00
abstract：:Hypoxic preconditioning protects photoreceptors against light-induced degeneration preserving retinal morphology and function. Although hypoxia inducible transcription factors 1 and 2 (HIF1, HIF2) are the main regulators of the hypoxic response, photoreceptor protection does not depend on HIF1 in rods. Here we used ro...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2015.12.008
更新日期：2016-05-01 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：:The aim of the study was to determine anatomical and growth factor profiles in patients with clinically significant macular oedema (CSMO) undergoing pars plana vitrectomy (PPV). Twenty patients with moderate nonproliferative diabetic retinopathy (NPDR) with persistent CSMO underwent PPV. Patients had baseline and post...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2005.10.002
更新日期：2006-05-01 00:00:00
abstract：:Hypoxia inducible factor (HIF) regulates expression of over 60 genes by binding to hypoxia response elements (HRE) located upstream of the transcriptional start sites. Many genes encoding proteins involved in iron transport and homeostasis are regulated by HIF. Expression of iron handling proteins can also be translat...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2014.05.010
更新日期：2014-08-01 00:00:00
abstract：:Photoreceptor cell pathology was investigated in an 8-yr-old mixed-breed dog which had displayed visual symptoms of 1 month duration. An electroretinogram detected no light-evoked responses. Light and electron microscopic features showed marked thinning and atrophy of the outer both the tapetal and non-tapetal retina ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(91)90095-v
更新日期：1991-03-01 00:00:00
abstract：:The distribution of collagen degradation and synthesis (turnover) between the central and peripheral areas of clear corneal allografts was determined, following transplantation of 6-mm [3H]proline-labelled corneal buttons from extensively pre-labelled, young rabbits into 13 nonradioactive mature rabbits. Control, cont...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(87)80076-3
更新日期：1987-07-01 00:00:00
abstract：:Myofibroblast development and haze generation in the corneal stroma is mediated by cytokines, including transforming growth factor-beta (TGF-beta), and possibly other cytokines. This study examined the effects of stromal PDGF-beta blockade on the development of myofibroblasts in response to -9.0 diopter photorefractiv...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2008.12.006
更新日期：2009-05-01 00:00:00
abstract：:The trabecular meshwork is considered a smooth muscle like tissue contributing to aqueous outflow regulation and thus to regulation of intraocular pressure. An elevation in intraocular pressure is one of the greatest risk factors for most forms of glaucoma. We assume that contraction of trabecular meshwork reduces aqu...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2004.12.013
更新日期：2005-06-01 00:00:00
abstract：:SLC4A11 mutations are associated with Fuchs' endothelial corneal dystrophy (FECD), congenital hereditary endothelial dystrophy (CHED) and Harboyan syndrome (endothelial dystrophy with auditory deficiency). Mice with genetically ablated Slc4a11 recapitulate CHED, exhibiting significant corneal edema and altered endothe...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2018.12.003
更新日期：2019-03-01 00:00:00
abstract：:Neuroretinal diseases are the predominant cause of irreversible blindness worldwide, mainly due to photoreceptor loss. Currently, there are no radical treatments to fully reverse the degeneration or even stop the disease progression. Thus, it is urgent to develop new biological therapeutics for these diseases on the c...
journal_title：Experimental eye research
pub_type： 杂志文章,评审
doi：10.1016/j.exer.2020.108283
更新日期：2021-01-01 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：:Phosducin is a retinal and pineal phosphoprotein assumed to play an important role in visual phototransduction. Phosducin is also a uveitopathogenic retinal antigen, but its potency has been reported to be mild. During the course of studies aimed at identifying uveitopathogenic sites in phosducin, we found that rat ph...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1997.0379
更新日期：1997-11-01 00:00:00
abstract：:Infection of the corneal endothelial cells by human cytomegalovirus (CMV) is an important cause of corneal endotheliitis. CMV endotheliitis is difficult to completely cure and relapses are frequent. This can cause blinding corneal bullous keratopathy. However, the pathogenesis of CMV endotheliitis remains undetermined...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2017.06.017
更新日期：2017-08-01 00:00:00
abstract：:Melanopsin is a non-image forming photoreceptor known to be present in the retina and it is considered to have light regulated tasks among other functions. In the present work, melanopsin presence in human lens epithelial cells as well as in human lens tissue is described for the first time. Moreover, studying the con...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2016.11.019
更新日期：2017-01-01 00:00:00
abstract：:Although primary cultures of human lens epithelial (HLE) cells provide important information concerning the role of epithelium in normal lens and cataract formation, the lack of a cell line precludes a broad range of studies on the metabolism and molecular biology of these cells. We have, therefore developed an HLE ce...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1998.0551
更新日期：1998-11-01 00:00:00
abstract：:Tears serve as a viable diagnostic fluid with advantages including less invasive sample to collect and less complex to prepare for analysis. Several water-soluble and fat-soluble vitamins were detected and quantified in human tears and compared with blood serum levels. Samples from 15 family pairs, each pair consistin...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2016.12.007
更新日期：2017-02-01 00:00:00
abstract：:Axial-length and refraction measurements are presented for the lid-sutured rhesus monkey at 6-month intervals during the first 1.5 years of life. The experimental data are fitted to an exponential growth theory allowing the calculation of time constants, apparent time origins, and correlation coefficients for 10 eyes ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(86)90043-6
更新日期：1986-06-01 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：:Previous studies have shown that the inhibition of Rho kinase is involved in the regulation of outflow facility in the live rabbit eye and the enucleated porcine eye. However, it is unknown whether the Rho kinase inhibition will do the same in non-human primates. To determine if the Rho kinase inhibitor Y-27632 will r...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2004.09.002
更新日期：2005-02-01 00:00:00
abstract：:The development and growth of the vertebrate ocular lens is dependent on the regulated proliferation of an anterior monolayer of epithelial cells, and their subsequent differentiation into elongate fiber cells. The growth factor rich ocular media that bathes the lens mediates these cellular processes, and their respec...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2018.02.012
更新日期：2018-05-01 00:00:00
