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Jing Xu, Lin-Jiang Chen, Jian Yu, Han-Jing Wang, Fan Zhang, Qiong Liu, Jing Wu
Diabetic retinopathy (DR) is a common and devastating microvascular complication of diabetes and a major cause of acquired blindness in young adults. Advanced glycation end products (AGEs) accumulated under hyperglycemic conditions are thought to play an important role in the pathogenesis of DR. AGEs can exert their deleterious effects by acting directly to induce aberrant crosslinking of extracellular matrix proteins, to increase vascular stiffness, altering vascular structure and function. Moreover, AGEs binding to the receptor for AGEs (RAGE) evokes intensive intracellular signaling cascades that leading to endothelial dysfunction, elaboration of key proinflammatory cytokines and proangiogenic factors, mediating pericyte apoptosis, vascular inflammation and angiogenesis, as well as breakdown of the inner blood-retinal barrier (BRB), the end result of all these events is damage to the neural and vascular components of the retina...
July 19, 2018: Cellular Physiology and Biochemistry
Kazuo Kunisawa, Takeshi Shimizu, Itaru Kushima, Branko Aleksic, Daisuke Mori, Yasuyuki Osanai, Kenta Kobayashi, Anna M Taylor, Manzoor A Bhat, Akiko Hayashi, Hiroko Baba, Norio Ozaki, Kazuhiro Ikenaka
Myelinated axons segregate the axonal membrane into four defined regions: the node of Ranvier, paranode, juxtaparanode and internode. The paranodal junction consists of specific component proteins, such as neurofascin155 (NF155) on the glial side, and Caspr and Contactin on the axonal side. Although paranodal junctions are thought to play crucial roles in rapid saltatory conduction and nodal assembly, the role of their interaction with neurons is not fully understood. In a previous study, conditional NF155 knockout in oligodendrocytes led to disorganization of the paranodal junctions...
July 19, 2018: Journal of Neurochemistry
Brian C Tse, Galina Dvoriantchikova, Wensi Tao, Ryan A Gallo, John Y Lee, Steven Pappas, Roberta Brambilla, Dmitry Ivanov, David T Tse, Daniel Pelaez
Purpose: To determine the effectiveness of etanercept, a tumor necrosis factor (TNF) inhibitor, in conferring neuroprotection to retinal ganglion cells (RGCs) and improving visual outcomes after optic nerve trauma with either optic nerve crush (ONC) or sonication-induced traumatic optic neuropathy (SI-TON) in mice. Methods: Mouse optic nerves were unilaterally subjected to ONC (n = 20) or SI-TON (n = 20). TNF expression was evaluated by using immunohistochemistry and quantitative RT-PCR (qRT-PCR) in optic nerves harvested 6 and 24 hours post ONC (n = 10) and SI-TON (n = 10)...
June 1, 2018: Investigative Ophthalmology & Visual Science
Ai Kido, Akihito Uji, Satoshi Morooka, Yoshimasa Kuroda, Shigeta Arichika, Tadamichi Akagi, Akitaka Tsujikawa
Purpose: Patients with Behcet's disease frequently have abnormal focal outer plexiform layer (OPL) bumps, which compress the inner nuclear layer. This study investigates the clinical relevance of these OPL elevations in Behcet's disease patients. Methods: Thirty-one consecutive patients (59 eyes) with Behcet's disease in remission and with available optical coherence tomography (OCT) images were included. The number of OPL bumps was counted using spectral-domain OCT images...
June 1, 2018: Investigative Ophthalmology & Visual Science
Merve Inanc Tekin, Mehmet Ali Sekeroglu, Canan Demirtas, Kemal Tekin, Sibel Doguizi, Serdar Bayraktar, Pelin Yilmazbas
Purpose: To determine brain-derived neurotrophic factor (BDNF) levels in serum and aqueous humor (AH) and to assess the relationship between BDNF levels and retinal layer thicknesses in age-related macular degeneration (AMD). Methods: A total of 48 AMD patients (AMD group) that was composed of twenty-three nonexudative and 25 exudative patients and 26 control subjects (control group) were included in the study. Serum and AH BDNF levels were assessed by ELISA method...
June 1, 2018: Investigative Ophthalmology & Visual Science
Bruce A Berkowitz, Robert H Podolsky, Benjamin Farrell, Hojun Lee, Christopher Trepanier, Ali M Berri, Kristin Dernay, Emma Graffice, Fatema Shafie-Khorassani, Timothy S Kern, Robin Roberts
Purpose: New perspectives are needed to understand decades of contradictory reports on the neuroprotective effects of the Cav1.2 L-type calcium channel blocker d-cis-diltiazem in retinitis pigmentosa (RP) models. Here, we address, in vivo, the following two knowledge gaps regarding d-cis-diltiazem's actions in the murine outer retina: (1) do normal mouse rods contain d-cis-diltiazem-insensitive Cav1.2 L-type calcium channels? (2) Can d-cis-diltiazem modify the normal rod redox environment? Methods: First, transretinal Cav1...
June 1, 2018: Investigative Ophthalmology & Visual Science
Hsiu-Mei Huang, Chao-Ching Huang, Meng-Han Tsai, Yi-Chieh Poon, Ying-Chao Chang
Purpose: Perinatal hypoxic-ischemic (HI) injury causes significant damages in the immature retina. The brain-derived neurotrophic factor is well known for its neuroprotective role but has limited clinical applications. A selective agonist of tyrosine kinase receptor B, 7,8-dihydroxyflavone (DHF), is a powerful therapeutic tool, when administered systemically. However, it remains unclear whether DHF treatment can protect the immature retinas against HI injury. Methods: Postnatal (P) day 7 rat pups were intraperitoneally injected with DHF or vehicle 2 hours before and 18 hours after being subjected to HI injury...
June 1, 2018: Investigative Ophthalmology & Visual Science
Jeong A Choi, Yoon Jeon Kim, Bo-Ra Seo, Jae-Young Koh, Young Hee Yoon
Purpose: We investigated whether zinc dyshomeostasis, a known mechanism of cell death in acute brain injury, contributes to the activation of matrix metalloproteinases (MMPs) and photoreceptor cell death in experimental retinal detachment (RD). Methods: RD was induced in mice by subretinal injection of 1:1 mixture of balanced salt solution and 1% sodium hyaluronate. On days 1 and 3 post RD, eyeballs were sectioned and examined for cell death (TUNEL staining), the degree of hypoxic insult (Hypoxyprobe staining), free zinc levels (TFL-Zn staining), and MMP-2 and -9 activity (gelatin zymography)...
June 1, 2018: Investigative Ophthalmology & Visual Science
Cody R Fisher, Deborah A Ferrington
AMD is the leading cause of blindness in developed countries. The dry form of AMD, also known as atrophic AMD, is characterized by the death of RPE and photoreceptors. Currently, there are no treatments for this form of the disease due in part to our incomplete understanding of the mechanism causing AMD. Strong experimental evidence from studies of human donors with AMD supports the emerging hypothesis that defects in RPE mitochondria drive AMD pathology. These studies, using different experimental methods, have shown disrupted RPE mitochondrial architecture and decreased mitochondrial number and mass, altered content of multiple mitochondrial proteins, increased mitochondrial DNA damage that correlates with disease severity, and defects in bioenergetics for primary RPE cultures from AMD donors...
March 20, 2018: Investigative Ophthalmology & Visual Science
Cirous Dehghani, Shaun Frost, Rajiv Jayasena, Colin L Masters, Yogesan Kanagasingam
Globally, Alzheimer's disease (AD) is a growing health and economic challenge that has no effective cure. Recent clinical trials indicate that preclinical treatment may be required but a routine screening tool for AD has been elusive. Hence, a simple, yet sensitive biomarker for preclinical AD, when the disease is most likely to be amenable to treatment, is lacking. Due to several features, the eye has been explored for this purpose and, among the ocular tissues, the retina has received the most attention. Currently, major works investigating the potential AD diagnosis by detecting amyloid-β (Aβ) signatures in the retinal tissue are underway, while the anterior eye is more accessible for in vivo imaging and examination...
July 2, 2018: Investigative Ophthalmology & Visual Science
Akira Sayo, Shinji Ueno, Taro Kominami, Satoshi Okado, Daiki Inooka, Shiori Komori, Hiroko Terasaki
Purpose: To determine the relationship between the sensitivity of the retina in the central 10° and the thickness of the retinal layers in patients with retinitis pigmentosa (RP). Methods: Fifty-two RP patients were studied. All of the patients had been examined by the Humphrey Field Analyzer 10-2 program (HFA10-2) and spectral-domain optical coherence tomography (SD-OCT). The thicknesses of the photoreceptor outer segment (OS), outer nuclear layer (ONL), inner nuclear layer (INL), and the retinal nerve fiber layer (RNFL) were measured at 1°, 3°, 5°, 7°, and 9° from the fovea...
July 2, 2018: Investigative Ophthalmology & Visual Science
Kelvin Yi Chong Teo, Shu Yen Lee, Amutha Veluchamy Barathi, Sai Bo Bo Tun, Licia Tan, Ian Jeffery Constable
Purpose: To determine if the surgical removal of the internal limiting membrane (ILM) in nonhuman primates (NHPs) will result in safe and effective transfection of adeno-associated viral (AAV2) vectors using green fluorescent protein (GFP) as a reporter. Methods: Six Macaca fascicularis NHP eyes underwent vitrectomy, ILM peel with layering of 1.7 × 1013 genome copies per milliliter of AAV2-GFP under air. Four control eyes underwent only vitrectomy and pooling under air...
July 2, 2018: Investigative Ophthalmology & Visual Science
Delu Song, Imran Mohammed, Rupak Bhuyan, Takashi Miwa, Allison Lesher Williams, Damodar Gullipalli, Sayaka Sato, Ying Song, Joshua L Dunaief, Wen-Chao Song
Purpose: Dense deposit disease (DDD) is caused by dysregulation of the alternative pathway of the complement cascade and characterized by electron-dense deposits in the kidney glomerular basement membrane (GBM) and drusen in Bruch's membrane (BrM). Complement factor H (fH) and factor properdin (fP) regulate complement activation; fH inhibits alternative pathway (AP) activation, whereas fP promotes it. We report pathologic changes in eyes of an fH and fP double-mutant mouse, which we previously showed have dense deposits in the GBM and early mortality from nephropathy...
July 2, 2018: Investigative Ophthalmology & Visual Science
Charandeep Singh, Amit Sharma, George Hoppe, Weilin Song, Youstina Bolok, Jonathan E Sears
Purpose: Transcriptional analysis of retina protected by hypoxia-inducible factor (HIF) stabilization demonstrates an increase in genes associated with aerobic glycolysis. We hypothesized that since protection is associated with a change in metabolism, oxygen-induced metabolites might transduce oxygen toxicity. We used global metabolic profiling to identify retinal metabolites increased in hyperoxia compared to normoxia. Methods: Untargeted gas chromatography mass spectroscopy (GC-MS) was performed on both mouse retina samples collected in hyperoxia and on primary human retinal endothelial cells, each with and without HIF stabilization...
July 2, 2018: Investigative Ophthalmology & Visual Science
Maria Vähätupa, Janika Nättinen, Antti Jylhä, Ulla Aapola, Marko Kataja, Peeter Kööbi, Tero A H Järvinen, Hannu Uusitalo, Hannele Uusitalo-Järvinen
Purpose: Oxygen-induced retinopathy (OIR) is the most widely used model for ischemic retinopathies such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and retinal vein occlusion (RVO). The purpose of this study was to perform the most comprehensive characterization of OIR by a recently developed technique, sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics. Methods: Control and OIR retina samples collected from various time points were subjected to SWATH-MS and detailed data analysis...
July 2, 2018: Investigative Ophthalmology & Visual Science
Anquan Xue, Linyan Zheng, Guilin Tan, Shaoqun Wu, Yue Wu, Lingyun Cheng, Jia Qu
Purpose: Myopia has become a global public health problem, particularly in East Asia where myopic retinopathy has become one of the leading causes of blindness and visual impairment in the elderly population. The purpose of this study was to evaluate the efficacy of posterior scleral contraction/reinforcement (PSCR) surgery on controlling the progressive elongation of axial length of highly myopic eyes in young patients. Methods: This is a prospective self-controlled interventional case series...
July 2, 2018: Investigative Ophthalmology & Visual Science
Mayu Moriguchi, Shinsuke Nakamura, Yuki Inoue, Anri Nishinaka, Maho Nakamura, Masamitsu Shimazawa, Hideaki Hara
Purpose: To determine the mechanism causing degeneration of the retinal pigment epithelium (RPE) and photoreceptors in mice after an intravenous injection of sodium iodate (NaIO3). Methods: The time-dependent changes in NaIO3-induced retinal degeneration were determined by analyzing the retinal morphology by optical coherence tomographic (OCT) images, histological sections of the retina, physiology of the retina by electroretinography (ERG), and retinal blood flow by laser speckle flowgraphy...
July 2, 2018: Investigative Ophthalmology & Visual Science
Michael J Allingham, Nomingerel Tserentsoodol, Peter Saloupis, Priyatham S Mettu, Scott W Cousins
Purpose: To determine the effects of aldosterone exposure on retinal edema and retinopathy in a mouse model of retinal vein occlusion (RVO). Methods: RVO was induced immediately following intravenous injection of Rose bengal (66 mg/kg) using a 532-nm wavelength laser to place three to seven applications at 80 mW and 50-μm spot size directed at the superior retinal vein one disc diameter away from the nerve. Negative control consisted of placing an equal number of laser spots without targeting the vein...
July 2, 2018: Investigative Ophthalmology & Visual Science
Ronald A J M Bierings, Marije H de Boer, Nomdo M Jansonius
Purpose: To determine whether the De Vries-Rose, Weber's, and Ferry-Porter's law, which describe visual performance as a function of luminance, also hold in patients with glaucoma. Methods: A case-control study with 19 glaucoma patients and 45 controls, all with normal visual acuity. We measured foveal and peripheral contrast sensitivity (CS) using static perimetry and foveal and peripheral critical fusion frequency (CFF; stimulus diameter 1°) as a function of luminance (0...
July 2, 2018: Investigative Ophthalmology & Visual Science
Xiao Xia Li, Zheng Zhang, Hui Yang Zeng, Shen Wu, Lu Liu, Jing Xue Zhang, Qian Liu, Di Ya Yang, Ning Li Wang
Purpose: To examine the early glial reactivity and neuron damage in response to short-term cerebrospinal fluid pressure (CSFp) reduction, as compared with intraocular pressure (IOP) elevation. Methods: The experiment included 54 male Sprague-Dawley rats with elevated translaminar cribrosa pressure difference (TLPD), defined as IOP minus CSFp. These rats underwent either continuous CSF drainage for 6 hours (n = 18), or unilateral IOP elevation to 40 mm Hg for 6 hours (n = 18)...
July 2, 2018: Investigative Ophthalmology & Visual Science
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