Abstract:
PURPOSE:The inhibition of angiogenesis by angiostatic steroids has been demonstrated in a variety of systems, including rabbit and rat cornea. There is considerable interest in the therapeutic potential of this class of compounds for angiogenic ocular conditions such as diabetic retinopathy, macular degeneration, and retinopathy of prematurity (ROP). This study was designed to test the capacity of an angiostatic steroid, anecortave acetate, to inhibit retinal neovascularization using a rat model of ROP and to investigate the mechanism of the effect. METHODS:At birth, rats were placed in an atmosphere of varying oxygen that produces retinal neovascular changes that approximate human ROP. The rats then received intravitreal injections of either anecortave acetate or vehicle at varying times, and all were subsequently placed in room air. Retinas were assessed for plasminogen activator inhibitor (PAI)-1 mRNA level by RNase protection assay at 1, 2, and 3 days after injection and for normal and abnormal blood vessel growth 3 days later. RESULTS:A significant reduction in the severity of abnormal retinal neovascularization was observed in the steroid-treated eyes compared with vehicle-injected eyes in ROP rats, yet the extent of normal total retinal vascular area was not significantly different. The drug had no effect on either retinal vascular area or neovascularization when tested in room air-raised control rats. Drug-injected eyes demonstrated a six- to ninefold increase in PAI-1 mRNA at 1 to 3 days after injection. CONCLUSIONS:This study represents the first therapeutic effect of an angiostatic steroid in an animal model of neovascular retinopathy. Additionally, the induction of PAI-1 indicates a mechanism of action for this class of compounds, and this is a novel finding in vivo. Because anecortave acetate significantly inhibited pathologic retinal angiogenesis in this model, while not significantly affecting normal intraretinal vessels, it holds therapeutic potential for a number of human ocular conditions in which angiogenesis plays a critical pathologic role.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Penn JS,Rajaratnam VS,Collier RJ,Clark AFkeywords:
subject
Has Abstractpub_date
2001-01-01 00:00:00pages
283-90issue
1eissn
0146-0404issn
1552-5783journal_volume
42pub_type
杂志文章abstract:PURPOSE:FGF-2 stimulates cell proliferation of rabbit corneal endothelial cells (rCECs) by degrading the cyclin-dependent kinase inhibitor p27(Kip1) (p27) through its phosphorylation mechanism. The authors investigated whether the cell proliferation of human CECs (hCECs) is also induced by FGF-2 stimulation through the...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-8213
更新日期:2011-10-17 00:00:00
abstract::PURPOSE. To define the role of the serine protease HTRA1 in age-related macular degeneration (AMD) by examining its expression level and identifying its potential substrates in the context of primary RPE cell extracellular milieu. METHODS. Primary RPE cell cultures were established from human donor eyes and screened f...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-4853
更新日期:2010-07-01 00:00:00
abstract:PURPOSE:Retinopathy of prematurity (ROP) is a major cause of visual handicap in the pediatric population. To date, this disorder is thought to stem from deficient retinal vascularization. Intriguingly, functional electrophysiological studies in patients with mild or moderate ROP and in the oxygen-induced retinopathy (O...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-6742
更新日期:2011-08-05 00:00:00
abstract:PURPOSE:To establish the regulatory roles that pericytes have in coordinating retinal endothelial cell (EC) growth and angiogenic potential. METHODS:Pericytes were derived from donor diabetic (DHuRP) or normal (NHuRP) human retinae, and characterized using vascular markers, coculture, contraction, morphogenesis, and p...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-13945
更新日期:2015-06-01 00:00:00
abstract:PURPOSE:Lens epithelial cells transdifferentiate to myofibroblasts during the formation of anterior subcapsular cataracts and secondary cataracts. One of the defining characteristics of myofibroblasts is the expression of alpha-smooth muscle actin (alpha-SMA). This study investigated some of the factors that influence ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2000-04-01 00:00:00
abstract:PURPOSE:China has among the lowest cataract surgical rates in Asia. This study was conducted to identify barriers to cataract surgery in rural China.
METHODS:All subjects having undergone cataract surgery and persons with presenting visual acuity
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,多中心研究
doi:10.1167/iovs.08-2783
更新日期:2009-03-01 00:00:00
abstract:PURPOSE:We compared the reproducibility and mutual agreement of the subfoveal choroidal thickness measurements by expert raters and an automated algorithm in enhanced depth imaging optical coherence tomography (EDI-OCT) images of eyes with nonneovascular age-related macular degeneration (AMD). METHODS:We recruited 44 ...
journal_title:Investigative ophthalmology & visual science
pub_type: 临床试验,杂志文章
doi:10.1167/iovs.12-11521
更新日期:2013-04-23 00:00:00
abstract:PURPOSE:To compare the mydriatic effect and the short-term corneal endothelial safety of intracamerally injected N-methyl-3,4-dihydroxyphenylamine (epinine) to phenylephrine in a porcine eye model. METHODS:One hundred twelve eyes from newly slaughtered pigs were used in this study. After pretreatment with 20 mg intrac...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-3651
更新日期:2009-11-01 00:00:00
abstract:PURPOSE:To further understand alpha2 receptor signaling in the retina and the mechanisms that mediate ocular beneficial effects of brimonidine (an alpha2 agonist) and nimodipine (an L-type Ca(2+) channel blocker). METHODS:The authors used in situ retinal ganglion cells (RGCs) in the isolated rat retina to characterize...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-4613
更新日期:2010-08-01 00:00:00
abstract:PURPOSE:In a group of humans with strabismic amblyopia, the relationship was examined between the structure and function of different brain regions. Three question were addressed: (1) Is the lateral geniculate nucleus (LGN) in humans with amblyopia structurally as well as functionally abnormal? (2) Do structural anomal...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-3931
更新日期:2010-03-01 00:00:00
abstract:PURPOSE:The increase in intraocular pressure in primary open-angle glaucoma (POAG) may involve transforming growth factor (TGF)-beta2 signaling, as TGF-beta2 is found in higher amounts than normal in the aqueous humor of patients with POAG. In vitro, TGF-beta2 causes an accumulation of extracellular matrix (ECM) in the...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-0226
更新日期:2007-02-01 00:00:00
abstract:Purpose:To examine the coaggregation and cohesion between the commonly isolated bacteria from contact lens cases. Methods:Four or five strains each of commonly isolated bacteria from contact lens cases, Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Serratia marcescens, were grown, wash...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-20593
更新日期:2017-01-01 00:00:00
abstract:PURPOSE:To define the inductive pathways leading to rat tear IgA antibody responses. METHODS:Fluoresceinated dinitrophenylated bovine serum albumin was encapsulated in poly(lactide-co-glycolide) microparticles and was administered by intranasal, ocular topical, or gastrointestinal routes. Histologic methods were used ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract:PURPOSE:To examine the effects of modification of immune effector cells, including macrophages, in the pathogenesis of herpes simplex virus retinitis in BALB/c mice. METHODS:Two intravitreal injections (2 microliters each) of anti-CD11b monoclonal antibody (mAb) [13 micrograms/microliters] were administered to the con...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract:PURPOSE:Na,K-adenosine triphosphatase (ATPase) is essential for the regulation of cytoplasmic ion concentrations in lens cells. Earlier studies demonstrated that tyrosine phosphorylation by Lyn kinase, a Src-family member, inhibits Na,K-ATPase activity in porcine lens epithelium. In the present study, experiments were ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-0809
更新日期:2005-02-01 00:00:00
abstract:PURPOSE:To isolate and characterize bovine lens endopeptidase activity that cleaves the Phe-Ser bond in peptide substrates. METHODS:The protease activity in young bovine lens homogenate was measured using the Mca-(Ala(7),Lys(Dnp)(9))-bradykinin substrate. Degradation of bradykinin and other unlabeled peptide substrate...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0769
更新日期:2004-04-01 00:00:00
abstract:PURPOSE:BM88 is a cell-cycle exit and neuronal differentiation protein that has been used as a marker of surviving retinal ganglion cells (RGCs) after optic nerve injury. Thy1.1 has also been used as a marker for RGC loss, but after optic nerve crush (ONC) a decrease in Thy1.1 expression precedes the loss of RGCs. The ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-12986
更新日期:2014-03-28 00:00:00
abstract:PURPOSE:To characterize a new nontransfected, spontaneously immortalized epithelial cell line from normal human conjunctiva (IOBA-NHC), both morphologically and functionally, to determine whether the differentiated phenotype of conjunctival epithelial cells is preserved. METHODS:Outgrowing cells from explanted conjunc...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0560
更新日期:2003-10-01 00:00:00
abstract:PURPOSE:The growth of ocular neovascularization is regulated by a balance between stimulating and inhibiting growth factors. Somatostatin affects angiogenesis by inhibiting the growth hormone-insulin-like growth factor axis and also has a direct antiproliferative effect on human retinal endothelial cells. The purpose o...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
abstract:PURPOSE:To determine the association between ocular dominance and spherical or astigmatic anisometropia, age, and sex. METHODS:Medical records of 10,264 myopic refractive surgery candidates were filtered. Ocular dominance was assessed with the hole-in-the-card test. Manifest refractive error was measured in each subje...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-8131
更新日期:2011-11-25 00:00:00
abstract:PURPOSE:The purpose of the present study was to investigate metabolic changes in different compartments of the rat lens (anterior, nuclear, posterior, and equatorial) after exposure to an acute double threshold dose of ultraviolet-B radiation (UVR-B) by using high-resolution magic angle spinning (HR-MAS) (1)H nuclear m...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1633
更新日期:2006-12-01 00:00:00
abstract:PURPOSE:To investigate the slow phase in latent/manifest latent nystagmus (LMLN) by producing long eye-drift intervals devoid of fast phases (extended slow phases [ESPs]) and to relate ESP metrics to clinical findings. METHODS:Ten patients with LMLN had eye movements recorded while attending to paired visual and audit...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0324
更新日期:2004-04-01 00:00:00
abstract:Purpose:We investigated whether fundus autofluorescence (FAF) lifetimes in patients with retinitis pigmentosa display a disease-specific lifetime pattern. Methods:Fundus autofluorescence lifetime imaging ophthalmoscopy (FLIO) was performed in two spectral channels (498-560 and 560-720 nm) after excitation with a 473 n...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-23336
更新日期:2018-04-01 00:00:00
abstract:PURPOSE:To identify proteins secreted by the retinal pigment epithelium (RPE) and to analyze their cellular distribution in normal and pathologic rat retinas at various stages of eye development. METHODS:A cDNA library was constructed with RNA isolated from porcine RPE sheets and screened by using the yeast signal seq...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-1048
更新日期:2004-05-01 00:00:00
abstract:PURPOSE:The role of macular pigment (MP) in age-related maculopathy (ARM) is still not clearly understood. Recent studies have reported on variations in the spatial distribution of MP optical density (MPOD) including a secondary peak ("ring") in the slope of the MPOD profile. The authors investigated in a cross-section...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-7610
更新日期:2011-10-11 00:00:00
abstract::Alloantigens placed into the anterior chamber of the eye elicit antigen-specific suppression of systemic delayed-type hypersensitivity (DTH) responses and severe impairment of skin allograft rejection. This pattern of immunologic alteration has been termed anterior chamber-associated immune deviation (ACAID) and is th...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
abstract:PURPOSE:In the Gbeta5(-/-) mouse, the electroretinogram (ERG) b-wave is absent, and the R7 subfamily of regulators of G protein signaling (RGS), which includes RGS6, -7, -9, and -11, is downregulated. Mutant mouse strains deficient in RGS7 or -11 were characterized, and the SG711 strain which is deficient in both prote...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-4084
更新日期:2010-02-01 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 investigate the molecular basis of hereditary lattice corneal dystrophy (LCD) type IIIA associated with corneal amyloid deposits afflicting several members of a four-generation family. METHODS:Histologic, immunohistochemical and biochemical studies were performed on corneal tissue samples obtained after per...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-1319
更新日期:2005-04-01 00:00:00
abstract:PURPOSE:To determine the prevalence, incidence, and progression of myopia of Chinese children in Hong Kong. METHODS:A cross-sectional survey was initially conducted. A longitudinal follow-up study was then conducted 12 months later. RESULTS:A total of 7560 children of mean age 9.33 (95% confidence interval [CI] = 9.1...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-1151
更新日期:2004-04-01 00:00:00