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https://www.readbyqxmd.com/read/28443635/expression-and-localisation-of-two-pore-domain-k2p-background-leak-potassium-ion-channels-in-the-mouse-retina
#1
Steven Hughes, Russell G Foster, Stuart N Peirson, Mark W Hankins
Two-pore domain (K2P) potassium channels perform essential roles in neuronal function. These channels produce background leak type potassium currents that act to regulate resting membrane potential and levels of cellular excitability. 15 different K2P channels have been identified in mammals and these channels perform important roles in a wide number of physiological systems. However, to date there is only limited data available concerning the expression and role of K2P channels in the retina. In this study we conduct the first comprehensive study of K2P channel expression in the retina...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442542/missense-mutations-in-the-wd40-domain-of-ahi1-cause-non-syndromic-retinitis-pigmentosa
#2
Thanh-Minh T Nguyen, Sarah Hull, Ronald Roepman, L Ingeborgh van den Born, Machteld M Oud, Erik de Vrieze, Lisette Hetterschijt, Stef J F Letteboer, Sylvia E C van Beersum, Ellen A Blokland, Helger G Yntema, Frans P M Cremers, Paul A van der Zwaag, Gavin Arno, Erwin van Wijk, Andrew R Webster, Lonneke Haer-Wigman
BACKGROUND: Recent findings suggesting that Abelson helper integration site 1 (AHI1) is involved in non-syndromic retinal disease have been debated, as the functional significance of identified missense variants was uncertain. We assessed whether AHI1 variants cause non-syndromic retinitis pigmentosa (RP). METHODS: Exome sequencing was performed in three probands with RP. The effects of the identified missense variants in AHI1 were predicted by three-dimensional structure homology modelling...
April 25, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28441398/the-effects-of-immune-protein-cd3%C3%AE-development-and-degeneration-of-retinal-neurons-after-optic-nerve-injury
#3
Tao He, Xavier Mortensen, Ping Wang, Ning Tian
Major histocompatibility complex (MHC) class I molecules and their receptors play fundamental roles in neuronal death during diseases. T-cell receptors (TCR) function as MHCI receptor on T-cells and both MHCI and a key component of TCR, CD3ζ, are expressed by mouse retinal ganglion cells (RGCs) and displaced amacrine cells. Mutation of these molecules compromises the development of RGCs. We investigated whether CD3ζ regulates the development and degeneration of amacrine cells after RGC death. Surprisingly, mutation of CD3ζ not only impairs the proper development of amacrine cells expressing CD3ζ but also those not expressing CD3ζ...
2017: PloS One
https://www.readbyqxmd.com/read/28441076/a-novel-neuroprotective-small-molecule-for-glial-cell-derived-neurotrophic-factor-induction-and-photoreceptor-rescue
#4
Petr Baranov, Hong Lin, Kathryn McCabe, David Gale, Shenshen Cai, Burke Lieppman, Dwight Morrow, Phoebe Lei, Justin Liao, Michael Young
PURPOSE: Degenerative diseases of the retina, such as retinitis pigmentosa and age-related macular degeneration, are characterized by the irreversible loss of photoreceptors. Several growth factors, including glial cell derived neurotrophic factor (GDNF), have been shown to rescue retinal neurons. An alternative strategy to direct GDNF administration is its induction in host retina by small molecules. Here we studied the ability of a novel small molecule GSK812 to induce GDNF in vitro/in vivo and rescue photoreceptors...
April 25, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28440245/pluripotent-stem-cells-a-therapeutic-source-for-age-related-macular-degeneration
#5
REVIEW
Sowmya Parameswaran, Subramanian Krishnakumar
Age-related macular degeneration (AMD) leads to progressive loss of central vision in the elderly. At a cellular level, there is aging of the retinal pigment epithelial (RPE) cells, and accumulation of lipofuscin that interferes with the proper functioning of RPE which eventually leads to apoptosis. Treatment depends on the stage of the disease. Wet AMD which has neovascularization is managed by local therapies such as laser photocoagulation and photodynamic therapy and is managed with injections of antivascular endothelial growth factor-based therapy...
March 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/28438678/do-photoreceptor-cells-cause-the-development-of-retinal-vascular-disease
#6
Timothy S Kern
The retinal vasculature is affected in a number of clinically important retinopathies, including diabetic retinopathy. There has been a considerable amount of research into the pathogenesis of retinal microvascular diseases, but the potential contribution of the most abundant cell population in the retina, photoreceptor cells, has been largely overlooked. This review summarizes ongoing research suggesting that photoreceptor cells play a critical role in the development of retinal vascular disease in diabetic retinopathy and other retinopathies...
April 21, 2017: Vision Research
https://www.readbyqxmd.com/read/28438165/microglia-derived-il-1%C3%AE-promotes-chemokine-expression-by-m%C3%A3-ller-cells-and-rpe-in-focal-retinal-degeneration
#7
Riccardo Natoli, Nilisha Fernando, Michele Madigan, Joshua A Chu-Tan, Krisztina Valter, Jan Provis, Matt Rutar
BACKGROUND: Chemokine signalling is required for the homing of leukocytes during retinal inflammation, and is associated with pathogenesis of diseases such as age-related macular degeneration (AMD). Here, we explore the role of interleukin-1β (IL-1β) in modulating AMD-associated chemokines Ccl2, Cxcl1, and Cxcl10 during photo-oxidative retinal damage, and the effect on both the accumulation of outer-retinal macrophages, and death of photoreceptors. METHODS: Inhibition of retinal IL-1β expression was performed using either siRNA or antibody neutralisation, which was intravitreally injected in SD rats prior to photo-oxidative damage...
April 24, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28436035/nap-counteracts-hyperglycemia-hypoxia-induced-retinal-pigment-epithelial-barrier-breakdown-through-modulation-of-hifs-and-vegf-expression
#8
Agata Grazia D'Amico, Grazia Maugeri, Daniela Maria Rasà, Valentina La Cognata, Salvatore Saccone, Concetta Federico, Sebastiano Cavallaro, Velia D'Agata
Diabetic macular edema (DME) is a common complication leading to a central vision loss in patients with diabetes. In this eye pathology, the hyperglycaemic/hypoxic microenvironment of pigmented epithelium is responsible for outer blood retinal barrier integrity changes. More recently, we have shown that a small peptide derived from the activity-dependent neuroprotective protein (ADNP), known as NAP, counteracts damages occurring during progression of diabetic retinopathy by modulating HIFs/VEGF pathway. Here, we have investigated for the first time the role of this peptide on outer blood retinal barrier (BRB) integrity exposed to hyperglycaemic/hypoxic insult mimicking a model in vitro of DME...
April 24, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28433754/mir-146a-suppresses-stat3-vegf-pathways-and-reduces-apoptosis-through-il-6-signaling-in-primary-human-retinal-microvascular-endothelial-cells-in-high-glucose-conditions
#9
Eun-Ah Ye, Jena J Steinle
microRNA (miRNA) play critical roles in the pathological processes of diabetic retinopathy, including inflammatory responses, insulin signaling, and angiogenesis. In addition to their regulatory functions on gene expression, miRNA is considered as a potential therapeutic target, as well as a diagnostic marker for many diseases. Our understanding on the pathological mechanisms underlying diabetic retinopathy is still incomplete and additional investigations are required to develop novel therapeutic strategies...
April 19, 2017: Vision Research
https://www.readbyqxmd.com/read/28433753/computational-image-analysis-for-prognosis-determination-in-dme
#10
Bianca S Gerendas, Hrvoje Bogunovic, Amir Sadeghipour, Thomas Schlegl, Georg Langs, Sebastian M Waldstein, Ursula Schmidt-Erfurth
In this pilot study, we evaluated the potential of computational image analysis of optical coherence tomography (OCT) data to determine the prognosis of patients with diabetic macular edema (DME). Spectral-domain OCT scans with fully automated retinal layer segmentation and segmentation of intraretinal cystoid fluid (IRC) and subretinal fluid of 629 patients receiving anti-vascular endothelial growth factor therapy for DME in a randomized prospective clinical trial were analyzed. The results were used to define 312 potentially predictive features at three timepoints (baseline, weeks 12 and 24) for best-corrected visual acuity (BCVA) at baseline and after one year used in a random forest prediction path...
April 19, 2017: Vision Research
https://www.readbyqxmd.com/read/28433627/docosahexaenoic-acid-promotes-differentiation-of-photoreceptor-cells-in-three-dimensional-neural-retinas
#11
Eisuke Arai, Vipul M Parmar, Bhubanananda Sahu, Lindsay Perusek, Tanu Parmar, Akiko Maeda
Retinal tissues generated from human pluripotent stem cells can be an excellent tool for investigating pathogenesis of retinal diseases and developing new pharmacologic therapies. Moreover, patient derived retinal tissues could allow for retinal transplantation therapy for degenerative retinal diseases. However, obtaining retinal tissues with matured photoreceptor outer segments, which are essential for photoreceptor functions, is currently challenging. Here we investigated the effects of docosahexaenoic acid (DHA) for maturation of photoreceptor outer segments at the late stage and visual chromophore analog, 9-cis-retinal for the early stage of differentiation to three-dimensional (3D)-retinal tissues from human embryonic stem cells (hESCs), respectively...
April 19, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28432360/functional-ectopic-neuritogenesis-by-retinal-rod-bipolar-cells-is-regulated-by-mir-125b-5p-during-retinal-remodeling-in-rcs-rats
#12
Yan Fu, Baoke Hou, Chuanhuang Weng, Weiping Liu, Jiaman Dai, Congjian Zhao, Zheng Qin Yin
Following retinal degeneration, retinal remodeling can cause neuronal microcircuits to undergo structural alterations, which particularly affect the dendrites of bipolar cells. However, the mechanisms and functional consequences of such changes remain unclear. Here, we used Royal College of Surgeon (RCS) rats as a model of retinal degeneration, to study structural changes in rod bipolar cells (RBCs) and the underlying mechanisms of these changes. We found that, with retinal degeneration, RBC dendrites extended into the outer nuclear layer (ONL) of the retina, and the ectopic dendrites formed synapses with the remaining photoreceptors...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432113/automated-quantitative-characterisation-of-retinal-vascular-leakage-and-microaneurysms-in-ultra-widefield-fluorescein-angiography
#13
Justis P Ehlers, Kevin Wang, Amit Vasanji, Ming Hu, Sunil K Srivastava
Ultra-widefield fluorescein angiography (UWFA) is an emerging imaging modality used to characterise pathology in the retinal vasculature such as microaneurysms (MAs) and vascular leakage. Despite its potential value for diagnosis and disease surveillance, objective quantitative assessment of retinal pathology by UWFA is currently limited because it requires laborious manual segmentation by trained human graders. In this report, we describe a novel fully automated software platform, which segments MAs and leakage areas in native and dewarped UWFA images with retinal vascular disease...
April 21, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28432111/regional-vascular-density-visual-field-sensitivity-relationship-in-glaucoma-according-to-disease-severity
#14
Joong Won Shin, Jiyun Lee, Junki Kwon, Jaewan Choi, Michael S Kook
AIMS: To study whether there are global and regional relationships between peripapillary vascular density (pVD) assessed by optical coherence tomography angiography (OCT-A) and visual field (VF) mean sensitivity at different glaucoma stages. METHODS: Microvascular images and peripapillary retinal nerve fibre layer (pRNFL) thicknesses were obtained using a Cirrus OCT-A device in 91 glaucoma subjects. The pVD was measured at various spatial locations according to the Garway-Heath map, using a MATLAB software (The MathWorks, Natick, Massachusetts)...
April 21, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28431867/whole-exome-sequencing-identification-of-novel-candidate-genes-in-patients-with-proliferative-diabetic-retinopathy
#15
Cindy Ung, Angie V Sanchez, Lishuang Shen, Samaneh Davoudi, Tina Ahmadi, Daniel Navarro-Gomez, Ching J Chen, Heather Hancock, Alan Penman, Suzanne Hoadley, Mark Consugar, Carlos Restrepo, Vinay A Shah, Joseph F Arboleda-Velasquez, Lucia Sobrin, Xiaowu Gai, Leo A Kim
Rare or novel gene variants in patients with proliferative diabetic retinopathy may contribute to disease development. We performed whole exome sequencing (WES) on patients at the phenotypic extremes of diabetic retinal complications: 57 patients diagnosed with proliferativediabetic retinopathy (PDR) as cases and 13 patients with no diabetic retinopathy despite at least 10 years of type 2 diabetes as controls. Thirty-one out of the 57 cases and all 13 controls were from the African American Proliferative Diabetic Retinopathy Study (AA)...
April 18, 2017: Vision Research
https://www.readbyqxmd.com/read/28430325/identification-of-a-disease-causing-mutation-in-a-chinese-patient-with-retinitis-pigmentosa-by-targeted-next-generation-sequencing
#16
Jianping Xiao, Xueqin Guo, Yong Wang, Mingkun Shao, Xiaoming Wei, Lique Du, Long Li, Yan Sun, Yun Yang
PURPOSE: To identify disease-causing mutations in a Chinese patient with retinitis pigmentosa (RP). METHODS: A detailed clinical examination was performed on the proband. Targeted next-generation sequencing (NGS) combined with bioinformatics analysis was performed on the proband to detect candidate disease-causing mutations. Sanger sequencing was performed on all subjects to confirm the candidate mutations and assess cosegregation within the family. RESULTS: Clinical examinations of the proband showed typical characteristics of RP...
April 14, 2017: European Journal of Ophthalmology
https://www.readbyqxmd.com/read/28429669/what-can-pharmacological-models-of-retinal-degeneration-tell-us
#17
M H Reisenhofer, J Balmer, V Enzmann
Animal models with pharmacologically induced retinal degeneration including sodium iodate (NaIO3) and N-methyl-N-nitrosourea (MNU) have been extensively used in ophthalmic research to investigate retinal degeneration. NaIO3 induces degeneration of the retinal pigment epithelium (RPE) followed by photoreceptor (PRC) cell death, mimicking features of age-related macular degeneration. In contrast, MNU leads to rapid destruction of the PRCs only, enabling the use of the MNU model to investigate degeneration induced in retinitis pigmentosa...
March 31, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28428895/suppression-of-retinal-neovascularization-by-inhibition-of-galectin-1-in-a-murine-model-of-oxygen-induced-retinopathy
#18
Ning Yang, Wenxi Zhang, Tao He, Yiqiao Xing
Galectin-1 (Gal-1) has been proved to be an important factor in the process of tumor angiogenesis recently. As a small molecule, OTX008 serves as a selective inhibitor of Gal-1. In this study, the role of Gal-1 and the antiangiogenic effect of OTX008 on retinal neovascularization (RNV) were investigated using a mouse model of oxygen-induced retinopathy. The outcome indicated that Gal-1 was overexpressed and closely related to retinal neovessels in OIR. After intravitreal injection of OTX008 at P12, the RNV was significantly reduced at P17, measuring by cross-sectional H&E staining and whole-mount fluorescence...
2017: Journal of Ophthalmology
https://www.readbyqxmd.com/read/28428049/stem-cells-for-retinal-disease-a-perspective-on-the-promise-and-perils
#19
Rajesh C Rao, Vaidehi S Dedania, Mark W Johnson
PURPOSE: To summarize key concepts, and early safety and efficacy signals from clinical trials for stem/progenitor cell-based interventions for retinal disease. DESIGN: Interpretive essay. METHODS: Review and synthesis of selected recent reports of stem/progenitor cell-based approaches for retinal disease, with interpretation and perspective. RESULTS: Stem/progenitor cell-based interventions represent a novel class of potential therapies for retinal diseases, such as age-related macular degeneration, inherited retinal dystrophies, and others...
April 17, 2017: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/28427069/practical-lessons-from-protocol-i-for-the-management-of-diabetic-macular-edema
#20
Lekha Mukkamala, Neelakshi Bhagat, Marco A Zarbin
Protocol I, a multicenter randomized clinical trial, compared the visual outcomes of patients treated with 0.5 mg intravitreal ranibizumab with either prompt or deferred (by 24 weeks laser), 4 mg intravitreal triamcinolone with prompt laser, or sham injection with prompt laser for the treatment of center-involving diabetic macular edema (DME). A total of 854 adult patients with type I or II diabetes and any level of non-proliferative diabetic retinopathy or proliferative retinopathy with adequate panretinal photocoagulation, with best-corrected visual acuity (BCVA) of 78 to 24 ETDRS letters (Snellen equivalent of 20/32 to 20/320) and visual loss attributed to macular edema, or retinal thickening with central subfield thickness of at least 250 µm by OCT were enrolled...
2017: Developments in Ophthalmology
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