Abstract:
PURPOSE:Glaucoma is an optic neuropathy commonly associated with elevated intraocular pressure (IOP), leading to optic nerve head (ONH) cupping, axon loss, and apoptosis of retinal ganglion cells (RGCs), which could ultimately result in blindness. Brn3b is a class-4 POU domain transcription factor that plays a key role in RGC development, axon outgrowth, and pathfinding. Previous studies suggest that a decrease in Brn3b levels occurs in animal models of glaucoma. The goal of this study was to determine if adeno-associated virus (AAV)-directed overexpression of the Brn3b protein could have neuroprotective effects following elevated IOP-mediated neurodegeneration. METHODS:Intraocular pressure was elevated in one eye of Brown Norway rats (Rattus norvegicus), following which the IOP-elevated eyes were intravitreally injected with AAV constructs encoding either the GFP (rAAV-CMV-GFP and rAAV-hsyn-GFP) or Brn3b (rAAV-CMV-Brn3b and rAAV-hsyn-Brn3b). Retina sections through the ONH were stained for synaptic plasticity markers and neuroprotection was assessed by RGC counts and visual acuity tests. RESULTS:Adeno-associated virus-mediated expression of the Brn3b protein in IOP-elevated rat eyes promoted an upregulation of growth associated protein-43 (GAP-43), actin binding LIM protein (abLIM) and acetylated α-tubulin (ac-Tuba) both posterior to the ONH and in RGCs. The RGC survival as well as axon integrity score were significantly improved in IOP-elevated rAAV-hsyn-Brn3b-injected rats compared with those of the IOP-elevated rAAV-hsyn-GFP- injected rats. Additionally, intravitreal rAAV-hsyn-Brn3b administration significantly restored the visual optomotor response in IOP-elevated rat eyes. CONCLUSIONS:Adeno-associated virus-mediated Brn3b protein expression may be a suitable approach for promoting neuroprotection in animal models of glaucoma.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Stankowska DL,Minton AZ,Rutledge MA,Mueller BH 2nd,Phatak NR,He S,Ma HY,Forster MJ,Yorio T,Krishnamoorthy RRdoi
10.1167/iovs.14-15008subject
Has Abstractpub_date
2015-01-13 00:00:00pages
893-907issue
2eissn
0146-0404issn
1552-5783pii
iovs.14-15008journal_volume
56pub_type
杂志文章abstract:PURPOSE:Peroxynitrite generated during the early phase of experimental autoimmune uveoretinitis (EAU) causes peroxidation of docosahexaenoic acid (22:6), a principal unsaturated fatty acid of the photoreceptor membrane, to its hydroperoxide (22:6HP). During this phase, microglia migrate to the site of photoreceptors. T...
journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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doi:
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abstract:PURPOSE:Müller cells support retinal neurons with essential functions. Here, we aim to examine the impact of starvation and oxidative stress on glutamate uptake and mitochondrial function in Müller cells. METHODS:Cultured human retinal Müller cells (MIO-M1) were exposed to H2O2 and additional starvation for 24 hours. ...
journal_title:Investigative ophthalmology & visual science
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更新日期:2016-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1998-10-01 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:
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abstract::The transport rates of radiolabeled ascorbic acid and dehydroascorbic acid, as well as, labeled 3-O-methyl-D-glucose and L-glucose from a central plasma compartment into aqueous and vitreous humors and cerebrospinal fluid were studied in vivo. Normal, male albino Sprague-Dawley rats and English Short Haired guinea pig...
journal_title:Investigative ophthalmology & visual science
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doi:
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abstract:PURPOSE:FOXC1 mutations result in Axenfeld-Rieger syndrome, a disorder characterized by a broad spectrum of malformations of the anterior segment of the eye and an elevated risk for glaucoma. A novel FOXC1 W152G mutation was identified in a patient with aniridia. Molecular analysis was conducted to determine the functi...
journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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更新日期:2019-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:2001-10-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2012-02-21 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1977-08-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
abstract::The authors created a new rabbit model for keratoconjunctivitis sicca by cauterizing the lacrimal gland excretory duct and surgically removing the nictitating membrane and harderian gland. Although the slit-lamp examination findings remained normal for the first 8 wk postoperatively, tear-film osmolarity was elevated ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1987-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1995-05-01 00:00:00
abstract:PURPOSE:To characterize reticular pseudodrusen (RPD) by using a point-to-point comparison of the reticular pattern on infrared reflectance (IR), autofluorescence (AF), and red-free (RF) images registered with en face sections of the choroid from spectral domain optical coherence tomography (SD-OCT) scans. METHODS:A cr...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-6942
更新日期:2011-07-29 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2010-12-01 00:00:00
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更新日期:2014-08-28 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2007-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,多中心研究
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更新日期:2019-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
abstract:Purpose:Vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in VEGF-induced angiogenesis. The goal of this project was to test the hypothesis that editing genomic VEGFR2 loci using the technology of clustered regularly interspaced palindromic repeats (CRISPR)-associated DNA endonuclease (Cas)9 in St...
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更新日期:2017-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2013-10-09 00:00:00
abstract:PURPOSE:The authors took advantage of the Oa1 mutant mouse in combination with other albinism mouse models (i.e., Tyrosinase and membrane-associated transporter protein [Matp]) to study the function of Oa1, the gene mutated in ocular albinism type 1, in the RPE during development and after birth. METHODS:Enzyme activi...
journal_title:Investigative ophthalmology & visual science
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更新日期:2005-12-01 00:00:00
abstract:PURPOSE:The purpose of this study was to determine whether human corneal epithelial cells and keratocytes synthesize both the soluble and membrane forms of the type II IL-1 receptor (IL-1RII). METHODS:Primary cell cultures of human corneal epithelial cells and keratocytes were established from human corneas. RT-PCR wa...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00