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Investigative Ophthalmology & Visual Science

Christina N Como, Andrew N Bubak, Anna M Blackmon, Dallas Jones, Niklaus H Mueller, Richard Davidson, Maria A Nagel
Purpose: While VZV DNA and antigen have been detected in acute and chronic VZV keratitis, it is unclear whether productive infection of corneal cells is ongoing or whether residual, noninfectious VZV antigens elicit inflammation. Herein, we examined VZV-infected primary human corneal epithelial cells (HCECs) and keratocytes (HKs) to elucidate the pathogenesis of VZV keratitis. Methods: HCECs and HKs were mock- or VZV infected. Seven days later, cells were examined for morphology, proinflammatory cytokine and matrix metalloproteinase (MMP) release, ability to recruit peripheral blood mononuclear cells (PBMCs) and neutrophils, and MMP substrate cleavage...
February 1, 2019: Investigative Ophthalmology & Visual Science
Ying Lin, Hong Jiang, Yi Liu, Giovana Rosa Gameiro, Giovanni Gregori, Chuanhui Dong, Tatjana Rundek, Jianhua Wang
Purpose: To determine age-related alterations in the retinal tissue perfusion (RTP) and volumetric vessel density (VVD) in healthy subjects. Methods: Total 148 healthy subjects (age 18 to 83 years) were enrolled and divided into four groups (G1, <35 years; G2, 35 ∼ 49 years; G3, 50 ∼ 64 years; and G4, ≥65 years). The RTP and VVD were measured at the macula. The RTP was calculated as the blood flow supplying the macular area (ϕ 2.5 mm) divided by the perfused tissue volume of the inner retina from the inner limiting membrane to the outer plexiform layer...
February 1, 2019: Investigative Ophthalmology & Visual Science
Satoshi Takeshima, Tomomi Higashide, Masayo Kimura, Sachiko Udagawa, Yutaro Yamada, Daisuke Takemoto, Shinji Ohkubo, Kazuhisa Sugiyama
Purpose: To investigate the effect of trabeculectomy on the waveform changes of laser speckle flowgraphy (LSFG) in the optic nerve head (ONH) in patients with glaucoma. Methods: Forty-eight eyes of 48 patients with open angle glaucoma were included in this prospective study. LSFG was performed before and 1, 3, and 6 months after trabeculectomy. Longitudinal changes in average mean blur rate (MBR), blow out score (BOS), resistivity index (RI), falling rate, skew, acceleration time index, and blow out time in the tissue area of the ONH were analyzed by using mixed-effects models...
February 1, 2019: Investigative Ophthalmology & Visual Science
Justin Ma, Peter Lwigale
Purpose: Defects in neural crest development are a major contributing factor in corneal dysgenesis, but little is known about the genetic landscape during corneal development. The purpose of this study was to provide a detailed transcriptome profile and evaluate changes in gene expression during mouse corneal development. Methods: RNA sequencing was used to uncover the transcriptomic profile of periocular mesenchyme (pNC) isolated at embryonic day (E) 10.5 and corneas isolated at E14...
February 1, 2019: Investigative Ophthalmology & Visual Science
Anil Tiwari, Sudha Swamynathan, Nicholas Alexander, John Gnalian, Shenghe Tian, Paul R Kinchington, Shivalingappa K Swamynathan
Purpose: Krüppel-like factor 4 (KLF4) promotes corneal epithelial (CE) cell fate while suppressing mesenchymal properties. TGF-β plays a crucial role in cell differentiation and development, and if dysregulated, it induces epithelial-mesenchymal transition (EMT). As KLF4 and TGF-β regulate each other in a context-dependent manner, we evaluated the role of the crosstalk between KLF4 and TGF-β-signaling in CE homeostasis. Methods: We used spatiotemporally regulated ablation of Klf4 within the adult mouse CE in ternary transgenic Klf4Δ/ΔCE (Klf4LoxP/LoxP/ Krt12rtTA/rtTA/ Tet-O-Cre) mice and short hairpin RNA (shRNA)-mediated knockdown or lentiviral vector-mediated overexpression of KLF4 in human corneal limbal epithelial (HCLE) cells to evaluate the crosstalk between KLF4 and TGF-β-signaling components...
February 1, 2019: Investigative Ophthalmology & Visual Science
Andrey V Dmitriev, Desmond Henderson, Robert A Linsenmeier
Purpose: The purpose of this study was to determine whether the ability of the rat retina to control its pH is affected by diabetes. Methods: Double-barreled H+-selective microelectrodes were used to measure extracellular [H+] in the dark-adapted retina of intact control and diabetic Long-Evans rats 1 to 6 months after intraperitoneal injection of vehicle or streptozotocin, respectively. Two manipulations-increasing of blood glucose and intravenous injection of the carbonic anhydrase blocker dorzolamide (DZM)-were used to examine their effects on retinal pH regulation...
February 1, 2019: Investigative Ophthalmology & Visual Science
Daniel B Russakoff, Ali Lamin, Jonathan D Oakley, Adam M Dubis, Sobha Sivaprasad
Purpose: To develop and assess a method for predicting the likelihood of converting from early/intermediate to advanced wet age-related macular degeneration (AMD) using optical coherence tomography (OCT) imaging and methods of deep learning. Methods: Seventy-one eyes of 71 patients with confirmed early/intermediate AMD with contralateral wet AMD were imaged with OCT three times over 2 years (baseline, year 1, year 2). These eyes were divided into two groups: eyes that had not converted to wet AMD (n = 40) at year 2 and those that had (n = 31)...
February 1, 2019: Investigative Ophthalmology & Visual Science
Peter L Nesper, Hee Eun Lee, Alaa E Fayed, Gregory W Schwartz, Fei Yu, Amani A Fawzi
Purpose: To assess retinal microvascular reactivity during dark adaptation and the transition to ambient light and after flicker stimulation using optical coherence tomography angiography (OCTA). Methods: Fifteen eyes of 15 healthy participants were dark adapted for 45 minutes followed by OCTA imaging in the dark-adapted state. After 5 minutes of normal lighting, subjects underwent OCTA imaging. Participants were then subjected to a flashing light-emitting diode (LED) light and repeat OCTA...
February 1, 2019: Investigative Ophthalmology & Visual Science
Guangying Luo, Xia Jing, Shuai Yang, Dewei Peng, Jing Dong, Li Li, Peter S Reinach, Dongsheng Yan
Purpose: DNA methylation is a key epigenetic modification involved in various biological processes and diseases. Corneal epithelial wound healing (CEWH) is essential for restoring corneal integrity and transparency after injury. However, the role of DNA methylation in CEWH remains elusive. Here, we investigate the function and underlying mechanism of DNA methylation in regulating CEWH. Methods: Dot blots and global methylation assays determined DNA methylation levels during CEWH...
February 1, 2019: Investigative Ophthalmology & Visual Science
Philippe M D'Onofrio, Alireza P Shabanzadeh, Brian K Choi, Mathias Bähr, Paulo D Koeberle
Purpose: Integrin adherence to the extracellular matrix (ECM) is essential for retinal ganglion cell (RGC) survival: damage causes production and release of ECM degrading matrix metalloproteinases (MMPs) that disrupt integrin ligation, leading to RGC death. The interplay of MMPs, integrins, and focal adhesion kinase (FAK) was studied in RGCs after optic nerve injury. Methods: Optic nerve transection and optic nerve crush were used to study RGC survival and regeneration, respectively...
February 1, 2019: Investigative Ophthalmology & Visual Science
Cherng-Ru Hsu, Yi-Hsun Chen, Chih-Peng Liu, Chih-Hung Chen, Kuo-Kuei Huang, Jui-Wen Huang, Meng-Nan Lin, Chih-Lung Lin, Wan-Ru Chen, Yi-Ling Hsu, Tze-Chung Lee, Shuen-Hsiang Chou, Chia-Mu Tu, Chrong-Shiong Hwang, Yu Chuan Huang, Da-Wen Lu
Purpose: The purpose of this study was to investigate the IOP-lowering effects of the ITRI-E-212, a new Rho-associated protein kinase (ROCK) inhibitor. ITRI-E-212 improved fluid outflow through the trabecular meshwork and reduced IOP with transient and mild conjunctival hyperemia. ITRI-E-212 can potentially be developed into new antiglaucoma agents. Methods: ITRI-E-212 was selected from more than 200 amino-isoquinoline structures because of its adequate solubility and drug-loading percentage in eye drops...
February 1, 2019: Investigative Ophthalmology & Visual Science
Cem Simsek, Takashi Kojima, Taeko Nagata, Murat Dogru, Kazuo Tsubota
Purpose: To evaluate the morphologic changes in the corneal subbasal nerve (CSN) plexus in wild-type (WT) mice after exposure to scopolamine-induced dry eye stress (DES) by using in vivo confocal microscopy. Methods: Twenty right eyes of twenty (n = 20) 8-week-old WT BALB/c male mice were investigated. The mice were divided into two experimental groups; 10 eyes of 10 mice exposed to DES for 28 days and 10 eyes of 10 mice were used as a control group. All mice underwent examinations for aqueous tear secretion quantity, tear film breakup time (TBUT), corneal vital staining...
February 1, 2019: Investigative Ophthalmology & Visual Science
Rachel Gater, Tugce Ipek, Salman Sadiq, Dan Nguyen, Lynval Jones, Alicia El Haj, Ying Yang
Purpose: Surgical techniques such as trabeculectomy aim to treat glaucoma by making an incision into the scleral tissue, to create an alternative drainage pathway for aqueous to flow into the sub-Tenon's/subconjunctival space. However, tissue fibrosis and wound healing occurring after the procedures can reduce the success rate. This study aims to investigate the synergistic effects of aqueous humor in combination with shear stress on the fibrosis response occurring in Tenon's capsule and conjunctival tissue (TCCT) after glaucoma surgery...
February 1, 2019: Investigative Ophthalmology & Visual Science
Won June Lee, Sung Uk Baek, Young Kook Kim, Ki Ho Park, Jin Wook Jeoung
Purpose: The purpose of this study was to determine the rate of ganglion cell-inner plexiform layer (GCIPL) thinning by Cirrus high-definition optical coherence tomography (HD-OCT) in normal eyes and open-angle glaucoma (OAG) and pseudoexfoliation glaucoma (PXG) eyes. Methods: This was a longitudinal observational study. We evaluated 282 subjects who visited a glaucoma clinic of a tertiary hospital in Korea: 60 healthy eyes, 193 medically treated OAG eyes, and 29 medically treated PXG eyes with a minimum 3-year follow-up involving serial spectral-domain OCT measurement of GCIPL thickness...
February 1, 2019: Investigative Ophthalmology & Visual Science
Jiwon Baek, Chui Ming Gemmy Cheung, Sohee Jeon, Jae Hyung Lee, Won Ki Lee
Purpose: We investigated the outer retinal, RPE, and choroidal changes and the development of choroidal neovascularization (CNV) in fellow eyes of patients with unilateral polypoidal choroidal vasculopathy or aneurysmal type 1 neovascularization (PCV/AT1). Methods: In this retrospective observational cohort study, 263 patients with unilateral PCV/AT1 were enrolled. Fundus photography, enhanced depth imaging optical coherence tomography, and indocyanine green angiography at baseline and follow-up were analyzed...
February 1, 2019: Investigative Ophthalmology & Visual Science
Yu Huang, Chea-Su Kee, Paul M Hocking, Cathy Williams, Shea Ping Yip, Jeremy A Guggenheim
Purpose: The rapid rise in prevalence over recent decades and high heritability of myopia suggest a role for gene-environment (G × E) interactions in myopia susceptibility. Few such G × E interactions have been discovered to date. We aimed to test the hypothesis that genetic analysis of susceptibility to visual experience-induced myopia in an animal model would identify novel G × E interaction loci. Methods: Chicks aged 7 days (n = 987) were monocularly deprived of form vision for 4 days...
February 1, 2019: Investigative Ophthalmology & Visual Science
Sasan Moghimi, Mona SafiZadeh, Masoud Aghsaei Fard, Nazgol Motamed-Gorji, Nassim Khatibi, Rebecca Chen, Robert N Weinreb
Purpose: To evaluate the changes in circumpapillary vessel density (cpVD) and retinal nerve fiber layer (RNFL) thickness after an acute primary angle closure (APAC) episode. Methods: Twenty-eight patients (28 pair of eyes) with unilateral APAC and 39 normal subjects (64 eyes) were included in this prospective, observational study. cpVD as measured by optical coherence tomography angiography and RNFL thickness as measured by spectral-domain optical coherence tomography were compared at 6 weeks after an APAC episode between affected, unaffected, and normal eyes...
February 1, 2019: Investigative Ophthalmology & Visual Science
D Grant Robinson, Tom H Margrain, Clare Bailey, Alison M Binns
Purpose: To evaluate the ability of visual function and structural tests to identify the likely risk of progression from early/intermediate to advanced AMD, using the Age-Related Eye Disease Study (AREDS) simplified scale as a surrogate for risk of progression. The secondary aim was to determine the relationship between disease severity grade and the observed functional and structural deficits. Methods: A total of 100 participants whose AMD status varied from early to advanced were recruited...
February 1, 2019: Investigative Ophthalmology & Visual Science
Mark K Webster, Betty J Barnett, Megan L Stanchfield, Joshua R Paris, Sarah E Webster, Cynthia A Cooley-Themm, Edward M Levine, Deborah C Otteson, Cindy L Linn
Purpose: The adult mammalian retina is typically incapable of regeneration when damaged by disease or trauma. Restoration of function would require generation of new adult neurons, something that until recently, mammals were thought to be incapable of doing. However, previous studies from this laboratory have shown that the α7 nicotinic acetylcholine receptor (α7 nAChR) agonist, PNU-282987, induces cell cycle reentry of Müller glia and generation of mature retinal neurons in adult rats, in the absence of detectible injury...
February 1, 2019: Investigative Ophthalmology & Visual Science
Daphné Silvestre, Angelo Arleo, Rémy Allard
Purpose: Vision decline with healthy aging is a major public health concern with the unceasing growth of the aged population. In order to prevent or remedy the age-related visual loss, a better understanding of the underlying causes is needed. The current psychophysical study used a novel noise paradigm to investigate the causes of age-related contrast sensitivity loss by estimating the impact of optical factors, absorption rate of photon by photoreceptors, neural noise, and calculation efficiency on contrast sensitivity...
February 1, 2019: Investigative Ophthalmology & Visual Science
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