Abstract:
PURPOSE:To investigate the effect of K-115, a novel Rho kinase (ROCK) inhibitor, on retinal ganglion cell (RGC) survival in an optic nerve crush (NC) model. Additionally, to determine the details of the mechanism of K-115's neuroprotective effect in vivo and in vitro. METHODS:ROCK inhibitors, including K-115 and fasudil (1 mg/kg/d), or vehicle were administered orally to C57BL/6 mice. Retinal ganglion cell death was then induced with NC. Retinal ganglion cell survival was evaluated by counting surviving retrogradely labeled cells and measuring RGC marker expression with quantitative real-time polymerase chain reaction (qRT-PCR). Total oxidized lipid levels were assessed with a thiobarbituric acid-reactive substances (TBARS) assay. Reactive oxygen species (ROS) levels were assessed by co-labeling with CellROX and Fluorogold. Expression of the NADPH oxidase (Nox) family of genes was evaluated with qRT-PCR. RESULTS:The survival of RGCs after NC was increased 34 ± 3% with K-115, a significantly protective effect. Moreover, a similar effect was revealed by the qRT-PCR analysis of Thy-1.2 and Brn3a, RGC markers. Levels of oxidized lipids and ROS also increased with time after NC. NC-induced oxidative stress, including oxidation of lipids and production of ROS, was significantly attenuated by K-115. Furthermore, expression of the Nox gene family, especially Nox1, which is involved in the NC-induced ROS production pathway, was dramatically reduced by K-115. CONCLUSIONS:The results indicated that oral K-115 administration delayed RGC death. Although K-115 may be mediated through Nox1 downregulation, we found that it did not suppress ROS production directly. Our findings show that K-115 has a potential use in neuroprotective treatment for glaucoma and other neurodegenerative diseases.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Yamamoto K,Maruyama K,Himori N,Omodaka K,Yokoyama Y,Shiga Y,Morin R,Nakazawa Tdoi
10.1167/iovs.13-13842subject
Has Abstractpub_date
2014-10-02 00:00:00pages
7126-36issue
11eissn
0146-0404issn
1552-5783pii
iovs.13-13842journal_volume
55pub_type
杂志文章abstract:PURPOSE:To investigate macular changes in acute retinopathy of prematurity (ROP). METHODS:Fifty-four premature infants with ROP and 20 controls underwent routine ROP screening with indirect ophthalmoscopy and imaging. A tabletop spectral domain optical coherence tomography (SD-OCT) scanner (Spectralis; Heidelberg Engi...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-7155
更新日期:2011-07-15 00:00:00
abstract:PURPOSE:To examine the possible presence of a major gene determining susceptibility to cortical cataract. METHODS:The percentage of the lens area involved with cortical opacity, summed over both eyes, was evaluated in 1275 individuals from the Beaver Dam Eye Study. After adjusting for the effects of age and sex, these...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::A group of 26 subjects with myotonic dystrophy were studied with fluorophotometry to evaluate the relationship between aqueous humor dynamics and the hypotony found in this disorder. All 26 received topical fluorescein to determine the anterior chamber elimination coefficient; five received systemic fluorescein to eva...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1982-06-01 00:00:00
abstract:PURPOSE:Autoimmune uveitis is a sight-threatening disease in which autoreactive T cells cross the blood-retinal barrier. Molecular mechanisms contributing to the loss of eye immune privilege in this autoimmune disease are not well understood. In this study, the authors investigated the changes in the matrix metalloprot...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-6475
更新日期:2011-04-08 00:00:00
abstract::The effects of x-rays and three chemical agents, known to cause intraocular inflammation in mammalian eyes, were studied on the chicken eye because this species was reported to be insensitive to the cataractogenic effects of x-rays. Intravitreal injection of Shigella endotoxin and topical and/or intravitreal administr...
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:Endocannabinoids are important modulators of synaptic transmission and plasticity throughout the central nervous system. The cannabinoid receptor type 1 (CB1R) is extensively expressed in the adult retina of rodents, while CB2R mRNA and protein expression have been only recently demonstrated in retinal tissue. ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-12514
更新日期:2013-12-11 00:00:00
abstract:PURPOSE:To determine whether polyamines are present in corneal cells, whether corneal cell polyamines can be depleted by blocking the first rate-limiting enzyme in the polyamine synthesis pathway, ornithine decarboxylase (ODC), and whether polyamines are required for proliferation in all three corneal cell types. METH...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.02-0889
更新日期:2003-06-01 00:00:00
abstract:Purpose:To determine if cytokine tear levels before hematopoietic stem cell transplantation (HSCT) can help anticipate the occurrence of ocular chronic graft-versus-host disease (cGVHD). Methods:In this pilot study, 25 patients undergoing HSCT were followed prospectively for ≤43 months. After ocular examinations, tear...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-21670
更新日期:2017-09-01 00:00:00
abstract:PURPOSE:Visibility of low-spatial frequency stimuli improves when their contrast is modulated at 5 to 10 Hz compared with stationary stimuli. Therefore, temporal modulations of visual objects could enhance the performance of low vision patients who primarily perceive images of low-spatial frequency content. We investig...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-9157
更新日期:2012-09-06 00:00:00
abstract:Purpose:To compare the phenotype of blue cone monochromacy (BCM) caused by large deletion mutations with those having the C203R missense mutation. Methods:BCM patients with large deletion mutations (n = 21; age range, 5-60 years), and with the C203R missense mutation (n = 13; age range, 5-70 years), were studied with ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.18-25280
更新日期:2018-12-03 00:00:00
abstract:Purpose:To investigate the effect of reducing high glucose (HG)-induced lysyl oxidase (LOX) overexpression and increased activity on retinal endothelial cell apoptosis. Methods:Rat retinal endothelial cells (RRECs) were grown in normal (N) or HG (30 mM glucose) medium for 7 days. In parallel, RRECs were grown in HG me...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-21340
更新日期:2017-05-01 00:00:00
abstract::Iron is a potent generator of oxidative damage whose levels increase with age, potentially exacerbating age-related diseases. Several lines of evidence suggest that iron accumulation may be a factor in age-related macular degeneration (AMD). AMD retinas have more iron within the photoreceptors, RPE, and drusen than do...
journal_title:Investigative ophthalmology & visual science
pub_type:
doi:10.1167/iovs.06-0568
更新日期:2006-11-01 00:00:00
abstract:Purpose:Epithelial to mesenchymal transition (EMT) is a cause of anterior and posterior subcapsular cataracts. Central to EMT is the formation of actin stress fibers. Selective targeting of actin stress fiber-associated tropomyosin (Tpm) in epithelial cells may be a means to prevent stress fiber formation and repress l...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.61.6.2
更新日期:2020-06-03 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::Cataracts in cultured rabbit lenses were produced by elevation of internal calcium. Experimental procedures were successful in increasing levels of total and bound Ca++, often without significant changes in sodium, potassium, or water content. Although the excess in calcium was predominantly associated with water-solu...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1982-02-01 00:00:00
abstract:PURPOSE:To examine the influence of experimentally reduced cerebrospinal fluid pressure (CSFP) on retinal nerve fiber layer (RNFL) thickness and neuroretinal rim area of the optic nerve head. METHODS:This experimental study included nine monkeys that underwent implantation of a lumbar-peritoneal cerebrospinal fluid (C...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-13657
更新日期:2014-04-15 00:00:00
abstract:PURPOSE:We evaluated the roles of tumor necrosis factor (TNF)-α in alkali-induced corneal neovascularization (CNV). METHODS:CNV was induced by alkali injury and compared in wild-type (WT) BALB/c mice, and TNF receptor 1-deficient (TNF-Rp55 KO) counterparts, or in mice treated with TNF-α antagonist and recombinant TNF-...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5548
更新日期:2012-06-14 00:00:00
abstract::The sequential electrophysiologic and pathologic changes in the retina in ceroid-lipofuscinosis were recorded in a time-course study in the ovine model. Over a relatively short period in the course of the disease, a severe reduction in both rod and cone b-wave amplitudes developed with rod b-wave changes preceeding th...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1984-03-01 00:00:00
abstract:PURPOSE:To determine, with the use of optical coherence tomography (OCT), the peripapillary retinal nerve fiber layer (RNFL) thickness among patients with retinitis pigmentosa (RP) of different degrees of disease severity. METHODS:One eye in each of 25 RP patients was included. All patients underwent complete ocular e...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-0404
更新日期:2007-10-01 00:00:00
abstract:PURPOSE:To develop an eye-motion-tracking optical coherence tomographic (OCT) method and assess its effect on image registration and nerve fiber layer (NFL) thickness measurement reproducibility. METHODS:A system capable of tracking common fundus features based on reflectance changes was integrated into a commercial O...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-0748
更新日期:2006-03-01 00:00:00
abstract:PURPOSE:To determine whether blood pressure and subclinical atherosclerosis are associated with incident age-related maculopathy (ARM). METHODS:The study was performed within the Rotterdam Study, a population-based, prospective cohort study in Rotterdam, The Netherlands. A total of 4822 subjects who at baseline were a...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0121
更新日期:2003-09-01 00:00:00
abstract::Cone electroretinograms were elicited with a full-field red flash after-45 min of dark adaptation from 16 patients with retinitis pigmentosa and from 17 normal subjects. The average latency and implicit time of the cone a-waves recorded from the patients were each significantly delayed (p less than 0.005) compared wit...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1981-11-01 00:00:00
abstract:Purpose:Synucleinopathies such as multiple system atrophy (MSA) and Parkinson's disease are associated with a variety of visual symptoms. Functional and morphological retinal aberrations are therefore supposed to be valuable biomarkers for these neurodegenerative diseases. This study examined the retinal morphology and...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.61.6.12
更新日期:2020-06-03 00:00:00
abstract:PURPOSE:T cells play an important role in the pathogenesis of uveitis. Recent studies have indicated that the TNFSF15 gene that encodes the TL1A protein can regulate the differentiation and activation of T cells. TNFSF15 gene polymorphisms have been found to be associated with several autoimmune disorders. A possible a...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-16896
更新日期:2015-07-01 00:00:00
abstract::The characterization of beta-adrenergic receptors on cultured human trabecular cells and trabecular meshwork from human autopsy eyes was carried out by radioligand binding utilizing (125I)-iodopindolol. In cultured cells, the observed binding of (125I)-iodopindolol was of high affinity (Kd = 43 pM) and saturable. Scat...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:The effects of adrenergic agonists and antagonists on Na+, K+, Cl- cotransport in fetal human nonpigmented ciliary epithelial (NPE) cells were investigated. METHODS:86Rb+ as a marker for K+ was used to study ouabain-insensitive, bumetanide-sensitive 86Rb+ uptake in cultured NPE monolayers. Cyclic adenosine mon...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::To compare the effects on the postnatal development of the eye of both total and partial form deprivation in diurnally reared chicks and of dark-rearing, chicks were reared with occluders covering one eye from hatching for up to 6 weeks. In diurnally reared birds, both total and partial form deprivation resulted in se...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract:PURPOSE:Skeletal and craniofacial muscles are frequently composed of multiple neuromuscular compartments that serve different physiological functions. Evidence of possible regional selectivity in LR intramuscular innervation was sought in a study of the anatomic potential of lateral rectus (LR) muscle compartmentalizat...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5330
更新日期:2010-09-01 00:00:00
abstract:PURPOSE:The authors compared the efficacy of two different forms of flicker perimetry: temporal modulation perimetry (TMP), which measures contrast thresholds for a fixed temporal frequency, and critical flicker frequency (CFF), which measures the highest frequency for which flicker is detected at a fixed contrast. ME...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1997-10-01 00:00:00
abstract:PURPOSE:The purpose of this study was to characterize a Krt12-Cre knock-in mouse line for corneal epithelium-specific gene ablation and to analyze the allelic selection of the keratin 12 (Krt12) gene during corneal type-epithelium differentiation. METHODS:Knock-in mice were generated by gene targeting. The authors exa...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5331
更新日期:2010-09-01 00:00:00