Abstract：
PURPOSE:The incidence of blindness is increasing, in part, because of abnormal ocular neovascularization. Anti-VEGF therapies have yielded impressive results; however, they are not a cure for blindness. Recently, metallothioneins (MTs) 1 and 2 have been implicated in the process of angiogenesis. Therefore, we investigated whether MT-1 and MT-2 were also involved in ocular neovascularization. METHODS:The concentrations of MT-1 and MT-2 (hereafter MT-1/2) were observed by ELISA. We examined the role of MT-1/2 in ocular neovascularization by using both an oxygen-induced retinopathy (OIR) model and a laser-induced choroidal neovascularization (CNV) model. We investigated the localization of MT-1/2 in retina. Furthermore, we investigated the expression of hypoxia-inducible factor (HIF)-1α and VEGF in OIR. In vitro, we investigated the degradation of HIF-1α. RESULTS:The MT-1/2 were significantly elevated in proliferative diabetic retinopathy patients. Ocular neovascularization, which was induced in both the OIR model and the CNV model, was decreased in MT-1/2 knockout (KO) mice. We confirmed that although MT-1/2 was expressed throughout the murine retina, its expression levels were highest in the endothelial cells. Further, OIR enhanced MT-1/2 expression in the retina. Interestingly, in the OIR model, both HIF-1α and VEGF levels were significantly decreased in the retina of MT-1/2 KO mice. In addition, we found that knockdown of MT-1/2 accelerated ubiquitination of HIF-1α. CONCLUSIONS:These results indicate that MT-1/2 are involved in retinal and choroidal neovascularization, and that MT-1/2 might be a new therapeutic target in diseases in which ocular angiogenesis is implicated.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Nakamura S,Shimazawa M,Inoue Y,Takata S,Ito Y,Tsuruma K,Ikeda T,Honda A,Satoh M,Hara Hdoi
10.1167/iovs.14-14545subject
Has Abstractpub_date
2014-09-23 00:00:00pages
6851-6860issue
10eissn
0146-0404issn
1552-5783pii
iovs.14-14545journal_volume
55pub_type
杂志文章abstract：PURPOSE:Strabismic amblyopia is typically associated with several visual deficits, including loss of contrast sensitivity in the amblyopic eye and abnormal binocular vision. Binocular summation ratios (BSRs) are usually assessed by comparing contrast sensitivity for binocular stimuli (sens(BIN)) with that measured in t...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.07-0194
更新日期：2007-11-01 00:00:00
abstract：PURPOSE:Angiogenesis, the formation of new capillary blood vessels, is an essential biological process under physiological conditions, including embryonic development, reproduction, and wound repair. Under pathologic conditions, this process plays a critical role in a variety of diseases such as cancer, rheumatoid arth...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.07-1527
更新日期：2008-09-01 00:00:00
abstract：PURPOSE:To identify the localization of indoleamine 2,3-dioxygenase (IDO) in human corneal cells and to evaluate its functional ability as a local immunosuppressive factor. METHODS:The expression profile of IDO was identified in primary cultures of human corneal cells (fibroblasts, epithelial cells, endothelial cells)...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.05-1336
更新日期：2007-09-01 00:00:00
abstract：PURPOSE:The purpose of this study was to modify and functionalize the surface of synthetic poly-ε-caprolactone (PCL) nanofibrous scaffolds to improve their biocompatibility in order to provide better "cell-substrate" interaction. METHODS:Poly-ε-caprolactone solution was electrospun and its surface functionality was mo...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.13-12727
更新日期：2014-02-12 00:00:00
abstract：Purpose:There is evidence that choroidal blood flow (ChBF) is regulated in a complex way during changes in ocular perfusion pressure (OPP). We hypothesized that ChBF regulates better in response to changes in mean arterial pressure (MAP) than in intraocular pressure (IOP). Methods:Eighteen volunteers (mean age, 26 yea...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章,随机对照试验
doi：10.1167/iovs.18-24992
更新日期：2019-01-02 00:00:00
abstract：PURPOSE:Intrastromal inlays for refractive correction of presbyopia are being adopted into clinical practice. An important concern is the effect of the inlay on the long-term health of the cornea due to disturbances in the concentration profiles of metabolic species. A three-dimensional metabolic model for the cornea i...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.13-13844
更新日期：2014-05-15 00:00:00
abstract：PURPOSE:Retinal basement membranes (BMs) serve as attachment sites for retinal pigment epithelial cells on Bruch's membrane and Müller cells (MCs) on the inner limiting membrane (ILM), providing polarity cues to adherent cells. The beta2 and gamma3 chains of laminin are key components of retinal BMs throughout developm...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.09-4645
更新日期：2010-03-01 00:00:00
abstract：:The phosphatic metabolite content of specific anatomic regions within the crystalline lens was determined by phosphorus-31 nuclear magnetic resonance analyses performed on tissue perchloric acid (PCA) extracts. Anatomically distinct zones each were dissected from five sets of 10 porcine lenses, isolated, and frozen in...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1985-04-01 00:00:00
abstract：PURPOSE:To identify cell types and extracellular matrix components in Molteno implant capsules. METHODS:Histologic features including cytology, distribution of apoptotic cells, cytoantigens, collagens, basement membranes, elastic fibers, and glycoproteins were examined by light microscopy. Findings were correlated wit...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.07-1424
更新日期：2009-03-01 00:00:00
abstract：PURPOSE:During early development, the ganglioside composition of the retina changes significantly, in that GD3 becomes the primary ganglioside in the mammalian retina. Because gangliosides play an important role in neuronal cell differentiation and proliferation, this change in ganglioside profile may indicate retinal ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.04-1439
更新日期：2005-07-01 00:00:00
abstract：PURPOSE:To obtain quantitative data on the optic disc excavation in children affected by cerebral visual impairment (CVI) by using the Heidelberg Retinal Tomograph (HRT)-II (Heidelberg Engineering, Heidelberg, Germany). METHODS:A total of 24 subjects affected by CVI (mean age, 7.28 years) were examined: 16 in alert co...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.05-0529
更新日期：2006-02-01 00:00:00
abstract：PURPOSE:When intraocular pressure (IOP) was monitored in supine healthy young adults throughout a 24-hour period, a diurnal-to-nocturnal elevation of IOP was observed. This study was undertaken to investigate whether a similar elevation of IOP can be detected when experimental subjects are in the sitting position. MET...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.03-0349
更新日期：2003-10-01 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：:Steady-state visual evoked potentials were elicited by the appearance/disappearance of sinusoidal gratings of varying spatial frequency for both eyes of amblyopic subjects. The amblyopic eyes showed reduced responses and a phase shift relative to the nonamblyopic eyes across a wide range of spatial frequencies. Both t...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1978-06-01 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 examine the expression of integrin vitronectin receptors (integrins alphavbeta3 and alphavbeta5) in native human fetal retinal pigment epithelium (RPE) and cultured hunman fetal RPE and to examine the role of RPE VnRs in the phagocytosis of photoreceptor rod outer segments (ROS). METHODS:Monoclonal antibodi...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1998-08-01 00:00:00
abstract：Purpose:Optical coherence tomography's (OCT) third outer retinal band has been attributed to the zone of interdigitation between RPE cells and cone outer segments. The purpose of this paper is to investigate the structure of this band with adaptive optics (AO)-OCT. Methods:Using AO-OCT, images were obtained from two s...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.16-21138
更新日期：2017-09-01 00:00:00
abstract：PURPOSE:To characterize the thickness profile of the corneal epithelium and the Bowman's layer across the horizontal meridian. METHODS:Forty-four eyes of 22 healthy subjects were investigated in this study. Ultra-high resolution anterior segment spectral domain-optical coherence tomography (SD-OCT) was used to assess ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.09-4748
更新日期：2011-06-01 00:00:00
abstract：PURPOSE:To determine the earliest changes that occur in the retina after the onset of ectopic expression of vascular endothelial growth factor (VEGF) by photoreceptors in transgenic mice, to characterize the development of neovascularization (NV), and to determine the feasibility of using these mice to test the efficac...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1998-01-01 00:00:00
abstract：PURPOSE:The influences of diurnal rhythms involving a variety of ocular parameters are implicated in the development of myopia. The purpose of this study was to determine the expression of the melatonin receptor subtype proteins in chick ocular tissues and to examine the role of the circadian signaling molecule melaton...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.05-0195
更新日期：2006-01-01 00:00:00
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journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2001-05-01 00:00:00
abstract：PURPOSE:To investigate the human disease due to CRB1 mutations and compare results with the Crb1-mutant rd8 mouse. METHODS:Twenty-two patients with CRB1 mutations were studied. Function was assessed with perimetry and electroretinography (ERG) and retinal structure with optical coherence tomography (OCT). Cortical str...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.11-7701
更新日期：2011-08-29 00:00:00
abstract：PURPOSE:To assess the thickness and surface area of porcine sclera. METHODS:One hundred twenty-eight porcine globes were sectioned from the center of the cornea to the region of the optic nerve. Photographs of the sectioned sclera including a millimeter scale were taken. Photographic slides were projected onto blank p...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2002-08-01 00:00:00
abstract：PURPOSE:To evaluate the efficacy of a biodegradable scleral plug containing ganciclovir (GCV) in a rabbit model of human cytomegalovirus (HCMV) retinitis. METHODS:To develop a rabbit model for HCMV retinitis, HCMV solution was injected once into the vitreous cavity of pigmented rabbits. The treated animals were divide...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：2001-08-01 00:00:00
abstract：PURPOSE:To evaluate macular focal cone ERG (fERG) as a tool for reliable and early detection of central retinal function decay in cone-rod dystrophy (CRD). METHODS:A retrospective study of the time course of fERG amplitude and its relation to visual acuity alterations was performed in 47 CRD patients followed yearly f...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.13-12676
更新日期：2013-10-09 00:00:00
abstract：PURPOSE:Microsaccades could indicate the place where our mind is unconsciously focusing, although our gaze is directed elsewhere. Many studies report the importance of microsaccades in visual scene perception, but none of them has addressed their relationship with the perception of a dynamic action and the prediction o...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.15-16880
更新日期：2015-07-01 00:00:00
abstract：PURPOSE:Recoverin has been identified as a target autoantigen for antirecoverin antibodies found in the sera of some patients with cancer-associated retinopathy. The aim of this study was to investigate the role of antirecoverin antibodies in cancer-associated retinopathy. METHODS:Human, rat, and rabbit antirecoverin ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1997-02-01 00:00:00
abstract：PURPOSE:To evaluate the efficiency, cell specificity, stability, and toxicity of recombinant adeno-associated virus (rAAV)-mediated retinal transduction in vivo in the adult immunocompetent mouse. To assess the usefulness of green fluorescent protein (GFP) for real-time, noninvasive monitoring of retinal transgene expr...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：
更新日期：1997-12-01 00:00:00
abstract：PURPOSE:Amphibian retinas regenerate after injury, making them ideal for studying the mechanisms of retinal regeneration, but this leaves their value as models of retinal degeneration in question. The authors asked whether the initial cellular changes after rod loss in the regenerative model Xenopus laevis mimic those ...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.10-5347
更新日期：2011-01-21 00:00:00
abstract：PURPOSE:To determine whether gene expression changes occur in the trabecular meshwork (TM) of cow eyes with steroid-induced intraocular pressure (IOP) elevation. METHODS:Adult female Braford cows (n = 4) were subjected to uniocular prednisolone acetate treatment for 6 weeks. IOP was monitored with an applanation tonom...
journal_title：Investigative ophthalmology & visual science
pub_type： 杂志文章
doi：10.1167/iovs.11-7563
更新日期：2011-11-07 00:00:00
