Abstract:
Purpose:Adult central nervous system (CNS) neurons are unable to regenerate their axons after injury. Krüppel-like transcription factor (KLF) family members regulate intrinsic axon growth ability in vitro and in vivo, but mechanisms downstream of these transcription factors are not known. Methods:Purified retinal ganglion cells (RGCs) were transduced to express exogenous KLF9, KLF16, KLF7, or KLF11; microarray analysis was used to identify downstream genes, which were screened for effects on axon growth. Dual-specificity phosphatase 14 (Dusp14) was further studied using genetic (siRNA, shRNA) and pharmacologic (PTP inhibitor IV) manipulation to assess effects on neurite length in vitro and survival and regeneration in vivo after optic nerve crush in rats and mice. Results:By screening genes regulated by KLFs in RGCs, we identified Dusp14 as a critical gene target limiting axon growth and regeneration downstream of KLF9's ability to suppress axon growth in RGCs. The KLF9-Dusp14 pathway inhibited activation of mitogen-activated protein kinases normally critical to neurotrophic signaling of RGC survival and axon elongation. Decreasing Dusp14 expression or disrupting its function in RGCs increased axon growth in vitro and promoted survival and optic nerve regeneration after optic nerve injury in vivo. Conclusions:These results link intrinsic and extrinsic regulators of axon growth and suggest modulation of the KLF9-Dusp14 pathway as a potential approach to improve regeneration in the adult CNS after injury.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Galvao J,Iwao K,Apara A,Wang Y,Ashouri M,Shah TN,Blackmore M,Kunzevitzky NJ,Moore DL,Goldberg JLdoi
10.1167/iovs.17-23319subject
Has Abstractpub_date
2018-06-01 00:00:00pages
2736-2747issue
7eissn
0146-0404issn
1552-5783pii
2683479journal_volume
59pub_type
杂志文章abstract:PURPOSE:Organized conjunctiva-associated lymphoid tissue (O-CALT) is constantly exposed to environmental antigens and plays a central role in the common mucosal immune system. This study was undertaken to investigate whether O-CALT in rabbit lymphoid tissue, as in other lymphoid tissue in other mammals, changes with ag...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-0856
更新日期:2008-02-01 00:00:00
abstract:PURPOSE:Equine recurrent uveitis (ERU) is an incurable disease affecting the inner eye that leads to blindness, through activated T cells that pass the blood-retinal barrier and destroy the retina. Serum markers are a desirable choice for monitoring development of disease, as serum is easy accessible and the markers co...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-4094
更新日期:2010-01-01 00:00:00
abstract:Purpose:To quantify and evaluate macular superficial capillaries and large vessels separately using an optical coherence tomographic angiography (OCTA)-based automatic segmentation algorithm. Methods:In this cross-sectional study, all eyes were scanned using an OCTA device with 3 × 3 mm cube centered on the fovea. Ret...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-23676
更新日期:2018-04-01 00:00:00
abstract:PURPOSE:The association of age and blood pressure (BP) with retinal vessel change is widely reported, with inverse relationships between retinal arteriolar and venular diameter and increasing age and elevated BP. No previous studies have dissected the separate effects of age and BP on the diameter of retinal vessels. ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-0893
更新日期:2007-02-01 00:00:00
abstract:Purpose:To evaluate spontaneous and evoked ocular sensory responses in rats after denervation of the lacrimal gland, as well as protein changes in tears that may mediate functional changes. Methods:Sprague-Dawley rats served as subjects. The left lacrimal gland was partially denervated with saporin toxin conjugated to...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.18-25267
更新日期:2018-10-01 00:00:00
abstract:PURPOSE:The aim of this study was to use Raman spectra of tears to differentiate between infectious and noninfectious ulcerative keratitis. METHODS:Raman microspectroscopy was applied using the drop-coating deposition method on Ti/Au-coated glass slides to obtain sample spectra from different human tear groups, includ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.11-7923
更新日期:2012-03-15 00:00:00
abstract::Patients with choroidal melanomas and simulating choroidal tumors were tested in a masked manner in a leukocyte-migration inhibition (LMI) assay with a 3M KCl antigen derived from a metastatic choroidal melanoma. Good discrimination petween patient groups was observed with this antigen. The sensitivity and specificity...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1977-02-01 00:00:00
abstract:PURPOSE:To identify pathogenic mutations in the guanylate cyclase-activating protein 1 (GCAP1) and GCAP2 genes and to characterize the biochemical effect of mutation on guanylate cyclase (GC) stimulation. METHODS:The GCAP1 and GCAP2 genes were screened by direct sequencing for mutations in 216 patients and 421 patient...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-0590
更新日期:2004-11-01 00:00:00
abstract:PURPOSE:The expression of the lens fiber cell integral membrane proteins MP20, the alpha 3 gap junction protein (connexin 46), and MP26 (MIP) was determined both during development of the bovine fetal lens and in different animal species. METHODS:The relative levels of the mRNA species coding for these proteins was de...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract:PURPOSE:To quantify protein changes in the morphologically distinct remodeling zone (RZ) and adjacent regions of the human lens outer cortex using spatially directed quantitative proteomics. METHODS:Lightly fixed human lens sections were deparaffinized and membranes labeled with fluorescent wheat germ agglutinin (WGA-...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-19791
更新日期:2016-08-01 00:00:00
abstract:PURPOSE:Vision restoration is a fast-approaching reality for some people with profound vision loss. In order to reliably determine treatment efficacy, accurate assessment of baseline residual visual function is critical. The purpose of this study was to compare residual function as detected on Goldman visual field (GVF...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-12657
更新日期:2014-03-06 00:00:00
abstract:PURPOSE:Extremely low gestational age neonates (ELGANs) requiring oxygen therapy often experience frequent episodes of intermittent hypoxia (IH) and are at high risk for severe retinopathy of prematurity (ROP). Using an established model for oxygen-induced retinopathy (OIR), we examined the hypothesis that there is a c...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.13-13040
更新日期:2013-11-19 00:00:00
abstract:PURPOSE:An alteration in corneal innervation has been described in dry eye associated with diabetes mellitus, contact lens use, and LASIK. The purpose of this study was to evaluate whether dry eye not related to Sjögren's syndrome (NSDE) and dry eye related to primary Sjögren's syndrome (PSDE) are associated with an al...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-0127
更新日期:2007-01-01 00:00:00
abstract:Purpose:To investigate the relationship between lens power and age as well as the relationship between lens power and axial length (AL) in Chinese children and adolescents. Methods:The participants underwent a comprehensive ophthalmic examination that included AL, cycloplegic refraction, and Pentacam measurements. The...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-22639
更新日期:2017-11-01 00:00:00
abstract:Purpose:Growing evidence suggests the involvement of the macula even in early stages of glaucoma. However, little is known about the impact of glaucomatous macular damage on central pattern vision. Here we examine the contrast requirement for letter recognition and its relationship with retinal thickness in the macular...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-22621
更新日期:2017-12-01 00:00:00
abstract:PURPOSE:To assess dynamic interactions of eye and head movements during return-sweep saccades (RSS) when reading with single-vision (SVL) versus progressive-addition (PAL) lenses in a simulated computer-based business environment. METHODS:Horizontal eye and head movements were recorded objectively and simultaneously a...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.02-0507
更新日期:2003-04-01 00:00:00
abstract:PURPOSE:To characterize photoreceptor cell apoptosis and cell loss in a mouse model of experimental retinal detachment (RD), and to use the technology of mouse genetics to study the molecular mechanisms underlying RD-associated photoreceptor degeneration. METHODS:Retinal detachments were created in adult wild-type and...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0827
更新日期:2004-02-01 00:00:00
abstract:PURPOSE:To test the hypothesis that longitudinal differences between retinal nerve fiber layer (RNFL) birefringence, measured by scanning laser polarimetry (SLP), and RNFL thickness, measured by optical coherence tomography (OCT), are informative about the state of axonal degeneration. METHODS:Colchicine was injected ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-0872
更新日期:2008-01-01 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:Disruption of the normally antiangiogenic environment of the retina leads to aberrant angiogenesis, the major cause of vision loss throughout the world. Prolactin (PRL), the hormone originally associated with milk production, can be proteolytically processed to 16K-PRL, a 16 kDa N-terminal PRL fragment with pot...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-0173
更新日期:2005-08-01 00:00:00
abstract::The effect of prostaglandin (PG) F2 alpha-isopropyl ester (IE), PGA2, or PGA2-IE on intraocular pressure (IOP) was tested in eight cynomolgus monkey eyes with argon laser-induced glaucoma. Dose-response testing and baseline IOP measurements were done. For multiple dose testing, 5 micrograms in 25 microliters (0.02%) o...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1990-11-01 00:00:00
abstract:PURPOSE:To investigate the specific role of myosin II, a critical biochemical determinant of cellular contraction, in modulation of aqueous humor outflow facility through the trabecular meshwork (TM) pathway. METHODS:Expression of the nonmuscle myosin II heavy chains (IIA, IIB, and IIC) in human TM and ciliary body (C...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-0164
更新日期:2005-11-01 00:00:00
abstract:PURPOSE:To quantify the prevalence and effect on visual acuity of macular cysts in a large cohort of patients with retinitis pigmentosa. METHODS:In 316 patients with typical forms of retinitis pigmentosa, visual acuity was measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts, macular cysts were dete...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.08-1992
更新日期:2008-10-01 00:00:00
abstract:PURPOSE:To investigate a depolarizing layer that is visible in polarization-sensitive optical coherence tomography (PS-OCT) images of the retina. To identify this layer and characterize its depolarizing effect quantitatively. METHODS:Ten healthy human subjects (mean age, 31 +/- 8 years) and two patients with RPE disea...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-1589
更新日期:2006-12-01 00:00:00
abstract:PURPOSE:This was a pilot study conducted to examine the expression of osteopontin in uveal melanoma and to determine whether serum osteopontin can be used in detecting metastatic uveal melanoma. METHODS:Osteopontin mRNA was measured in three uveal melanoma cell lines of various invasive potential by real-time PCR. Tis...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.05-0422
更新日期:2006-03-01 00:00:00
abstract:PURPOSE:By their control of membrane potential and intracellular free Ca(2+) ([Ca(2+)](i)), K(+) currents are pivotal in the regulation of arterial smooth muscle tone. The goal of the present study was to identify and characterize the A-type K(+) current in retinal microvascular smooth muscle (MVSM) and to examine its ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-1465
更新日期:2005-09-01 00:00:00
abstract:Purpose:The purpose of this study was to clarify the interactions between macrophages (MPs) and RPE cells in coculture systems to investigate the functional plasticity of RPE cells. Methods:Adherent peritoneal cells or murine MP cell line Raw 264.7 was cocultured with primary RPE cells taken from C57BL/6 mice, with or...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-20604
更新日期:2016-11-01 00:00:00
abstract:PURPOSE:Diabetes reduces retinal and visual sensitivity to dim light flashes. However, the impact of diabetes on contrast sensitivity in dim light is unknown. Based on the lowered visual sensitivity previously observed, we hypothesized that contrast sensitivity would similarly be reduced. We therefore examined scotopic...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.12-10825
更新日期:2013-02-28 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:Glaucoma is the second most frequent cause of visual impairment worldwide. Elevated intraocular pressure (IOP) causes glaucomatous optic nerve damage, especially in the primary open-angle glaucoma (POAG) subtype. As most previous studies on IOP genetics were analyses of glaucomatous families, a study of general...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-3979
更新日期:2010-03-01 00:00:00