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https://www.readbyqxmd.com/read/28534762/aiding-the-eye-watching-the-brain-james-weiland-ieee-fellow-explores-the-unique-challenges-of-retinal-prostheses
#1
Kristina Grifantini
The retina is a sophisticated neural network that provides humans with high-resolution vision. And for those who suffer from retinal disease or deterioration, particularly age-related macular degeneration (the leading cause of blindness among people over the age of 50 in the United States), a better understanding of how to stimulate the retina or completely override its path to the area of the brain that processes vision may offer hope to restore sight.
May 2017: IEEE Pulse
https://www.readbyqxmd.com/read/28532361/electrical-stimulation-of-the-retina-to-produce-artificial-vision
#2
James D Weiland, Steven T Walston, Mark S Humayun
Retinal prostheses aim to restore vision to blind individuals suffering from retinal diseases such as retinitis pigmentosa and age-related macular degeneration. These devices function by electrically stimulating surviving retinal neurons, whose activation is interpreted by the brain as a visual percept. Many prostheses are currently under development. They are categorized as epiretinal, subretinal, and suprachoroidal prostheses on the basis of the placement of the stimulating microelectrode array. Each can activate ganglion cells through direct or indirect stimulation...
October 14, 2016: Annual Review of Vision Science
https://www.readbyqxmd.com/read/28529701/recent-advances-in-the-management-of-dry-age-related-macular-degeneration-a-review
#3
REVIEW
Francesco Bandello, Riccardo Sacconi, Lea Querques, Eleonora Corbelli, Maria Vittoria Cicinelli, Giuseppe Querques
Age-related macular degeneration (AMD), the most important cause of vision loss in elderly people, is a degenerative disorder of the central retina with a multifactorial etiopathology. AMD is classified in dry AMD (d-AMD) or neovascular AMD depending on the presence of choroidal neovascularization. Currently, no therapy is approved for geographic atrophy, the late form of d-AMD, because no treatment can restore the damage of retinal pigment epithelium (RPE) or photoreceptors. For this reason, all treatment approaches in d-AMD are only likely to prevent and slow down the progression of existing atrophy...
2017: F1000Research
https://www.readbyqxmd.com/read/28526489/intravitreous-injection-of-aav2-sflt01-in-patients-with-advanced-neovascular-age-related-macular-degeneration-a-phase-1-open-label-trial
#4
Jeffrey S Heier, Saleema Kherani, Shilpa Desai, Pravin Dugel, Shalesh Kaushal, Seng H Cheng, Cheryl Delacono, Annie Purvis, Susan Richards, Annaig Le-Halpere, John Connelly, Samuel C Wadsworth, Rafael Varona, Ronald Buggage, Abraham Scaria, Peter A Campochiaro
BACKGROUND: Long-term intraocular injections of vascular endothelial growth factor (VEGF)-neutralising proteins can preserve central vision in many patients with neovascular age-related macular degeneration. We tested the safety and tolerability of a single intravitreous injection of an AAV2 vector expressing the VEGF-neutralising protein sFLT01 in patients with advanced neovascular age-related macular degeneration. METHODS: This was a phase 1, open-label, dose-escalating study done at four outpatient retina clinics in the USA...
May 16, 2017: Lancet
https://www.readbyqxmd.com/read/28515072/%C3%AF-3-and-%C3%AF-6-long-chain-pufas-and-their-enzymatic-metabolites-in-neovascular-eye-diseases
#5
REVIEW
Yan Gong, Zhongjie Fu, Raffael Liegl, Jing Chen, Ann Hellström, Lois Eh Smith
Neovascular eye diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, threaten the visual health of children and adults. Current treatment options, including anti-vascular endothelial growth factor therapy and laser retinal photocoagulation, have limitations and are associated with adverse effects; therefore, the identification of additional therapies is highly desirable. Both clinical and experimental studies show that dietary ω-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFAs) reduce retinal and choroidal angiogenesis...
May 17, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28507131/involvement-of-a-gut-retina-axis-in-protection-against-dietary-glycemia-induced-age-related-macular-degeneration
#6
Sheldon Rowan, Shuhong Jiang, Tal Korem, Jedrzej Szymanski, Min-Lee Chang, Jason Szelog, Christa Cassalman, Kalavathi Dasuri, Christina McGuire, Ryoji Nagai, Xue-Liang Du, Michael Brownlee, Naila Rabbani, Paul J Thornalley, James D Baleja, Amy A Deik, Kerry A Pierce, Justin M Scott, Clary B Clish, Donald E Smith, Adina Weinberger, Tali Avnit-Sagi, Maya Lotan-Pompan, Eran Segal, Allen Taylor
Age-related macular degeneration (AMD) is the major cause of blindness in developed nations. AMD is characterized by retinal pigmented epithelial (RPE) cell dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate important contributions of dietary patterns to the risk for AMD, but the mechanisms relating diet to disease remain unclear. Here we investigate the effect on AMD of isocaloric diets that differ only in the type of dietary carbohydrate in a wild-type aged-mouse model. The consumption of a high-glycemia (HG) diet resulted in many AMD features (AMDf), including RPE hypopigmentation and atrophy, lipofuscin accumulation, and photoreceptor degeneration, whereas consumption of the lower-glycemia (LG) diet did not...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28506260/atypical-retinal-pigment-epithelial-defects-with-retained-photoreceptor-layers-a-so-far-disregarded-finding-in-age-related-macular-degeneration
#7
Helena Giannakaki-Zimmermann, Giuseppe Querques, Inger Christine Munch, Daraius Shroff, David Sarraf, Xuejing Chen, Eduardo Cunha-Souza, Sarah Mrejen, Vittorio Capuano, Murilo W Rodrigues, Charu Gupta, Andreas Ebneter, Martin S Zinkernagel, Marion R Munk
BACKGROUND: To report patients with age-related macular degeneration and atypical central retinal pigment epithelium (RPE) defects not attributable to geographic atrophy (GA) or RPE-tears with overlying preserved photoreceptor layers. METHODS: Multimodal imaging case-series evaluating the course of atypical RPE- defects in patients with AMD using Color fundus images, Optical coherence tomography (OCT), OCT-Angiography, fundus autofluorescence (FAF) and fluorescein-angiography (FA)...
May 15, 2017: BMC Ophthalmology
https://www.readbyqxmd.com/read/28486987/progress-of-stem-progenitor-cell-based-therapy-for-retinal-degeneration
#8
REVIEW
Zhimin Tang, Yi Zhang, Yuyao Wang, Dandan Zhang, Bingqiao Shen, Min Luo, Ping Gu
Retinal degeneration (RD), such as age-related macular degeneration (AMD) and retinitis pigmentosa, is one of the leading causes of blindness. Presently, no satisfactory therapeutic options are available for these diseases principally because the retina and retinal pigmented epithelium (RPE) do not regenerate, although wet AMD can be prevented from further progression by anti-vascular endothelial growth factor therapy. Nevertheless, stem/progenitor cell approaches exhibit enormous potential for RD treatment using strategies mainly aimed at the rescue and replacement of photoreceptors and RPE...
May 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28482029/from-compliment-to-insult-genetics-of-the-complement-system-in-physiology-and-disease-in-the-human-retina
#9
Robert F Mullins, Alasdair N Warwick, Elliott H Sohn, Andrew J Lotery
Age-related macular degeneration (AMD) is a major cause of visual impairment that affects the central retina. Genome wide association studies and candidate gene screens have identified members of the complement pathway as contributing to the risk of AMD. In this review, we discuss the complement system, its importance in retinal development and normal physiology, how its dysregulation may contribute to disease, and how it might be targeted to prevent damage to the aging choriocapillaris in AMD.
May 8, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28480968/the-influence-of-raav2-mediated-sox2-delivery-into-neonatal-and-adult-human-rpe-cells-a-comparative-study
#10
Razie Ezati, Azadeh Etemadzadeh, Zahra-Soheila Soheili, Shahram Samiei, Ehsan Ranaei Pirmardan, Malihe Davari, Hoda Shams Najafabadi
Cell replacement is a promising therapy for degenerative diseases like age-related macular degeneration (AMD). Since the human retina lacks regeneration capacity, much attention has been directed towards persuading for cells that can differentiate into retinal neurons. In this report we have investigated reprogramming of the human RPE cells and concerned the effect of donor age on the cellular fate as a critical determinant in reprograming competence. We evaluated the effect of SOX2 over-expression in human neonatal and adult RPE cells in cultures...
May 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28477014/anti-complement-component-5-antibody-targeting-mg4-domain-inhibits-choroidal-neovascularization
#11
Dong Hyun Jo, Jin Hyoung Kim, Wonjun Yang, Hyori Kim, Shinjae Chang, Dongjo Kim, Minseok Chang, Kihwang Lee, Junho Chung, Jeong Hun Kim
Age-related macular degeneration (AMD) is one of the main causes of visual impairment in adults. Visual deterioration is more prominent in neovascular AMD with choroidal neovascularization (CNV). Clinical and postmortem studies suggested that complement system activation might induce CNV. In this study, we demonstrated that an anti-mouse complement component 5 (C5) antibody targeting MG4 domain of β chain effectively inhibited CNV which was induced by laser photocoagulation in mice. The targeted epitope of this anti-C5 antibody was different from that of currently utilized anti-C5 antibody (eculizumab) in the MG7 domain in which a single nucleotide polymorphism (R885H/C) results in poor response to eculizumab...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28475704/combined-fundus-autofluorescence-and-near-infrared-reflectance-as-prognostic-biomarkers-for-visual-acuity-in-foveal-sparing-geographic-atrophy
#12
Moritz Lindner, Jennifer Nadal, Matthias M Mauschitz, Anna Lüning, Joanna Czauderna, Maximilian Pfau, Steffen Schmitz-Valckenberg, Frank G Holz, Matthias Schmid, Monika Fleckenstein
Purpose: To identify predictors of best corrected visual acuity (BCVA) in eyes with foveal-sparing geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Methods: Best corrected visual acuity (Early Treatment Diabetic Retinopathy Study charts); serial fundus autofluorescence; and near-infrared reflectance images of patients participating in the FAM (NCT00393692) and DSGA (NCT02051998) studies were analyzed. The sizes of GA and spared fovea, and the minimal linear dimension of intact retinal pigment epithelium ("bridge") between the residual foveal island and the surrounding retina were quantified and associations with BCVA were assessed by local regression curves and mixed effects models...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28471458/comprehensive-analysis-of-mouse-retinal-mononuclear-phagocytes
#13
Anika Lückoff, Rebecca Scholz, Florian Sennlaub, Heping Xu, Thomas Langmann
The innate immune system is activated in a number of degenerative and inflammatory retinal disorders such as age-related macular degeneration (AMD). Retinal microglia, choroidal macrophages, and recruited monocytes, collectively termed 'retinal mononuclear phagocytes', are critical determinants of ocular disease outcome. Many publications have described the presence of these cells in mouse models for retinal disease; however, only limited aspects of their behavior have been uncovered, and these have only been uncovered using a single detection method...
June 2017: Nature Protocols
https://www.readbyqxmd.com/read/28461502/mef2d-haploinsufficiency-downregulates-the-nrf2-pathway-and-renders-photoreceptors-susceptible-to-light-induced-oxidative-stress
#14
Saumya Nagar, Sarah M Noveral, Dorit Trudler, Kevin M Lopez, Scott R McKercher, Xuemei Han, John R Yates, Juan C Piña-Crespo, Nobuki Nakanishi, Takumi Satoh, Shu-Ichi Okamoto, Stuart A Lipton
Gaining mechanistic insight into interaction between causative factors of complex multifactorial diseases involving photoreceptor damage might aid in devising effective therapies. Oxidative stress is one of the potential unifying mechanisms for interplay between genetic and environmental factors that contribute to photoreceptor pathology. Interestingly, the transcription factor myocyte enhancer factor 2d (MEF2D) is known to be important in photoreceptor survival, as knockout of this transcription factor results in loss of photoreceptors in mice...
May 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28451952/a-systematic-review-of-the-treat-and-extend-treatment-regimen-with-anti-vegf-agents-for-neovascular-age-related-macular-degeneration
#15
REVIEW
Maria Gemenetzi, Praveen J Patel
Despite significant progress in retaining vision for neovascular age-related macular degeneration patients in the era of treatment with intravitreal anti-VEGF agents, there is no universally accepted treatment regimen that defines the frequency of treatment needed to achieve the optimal visual outcomes while simultaneously balancing the burden of long-term, frequent and high-cost treatment. Treat and extend has recently and consistently been used by retina specialists to minimise the financial and psychological costs of the need for frequent treatment with anti-VEGF injections...
April 27, 2017: Ophthalmology and Therapy
https://www.readbyqxmd.com/read/28442885/complement-c5a-receptor-knockout-has-diminished-light-induced-microglia-macrophage-retinal-migration
#16
Delu Song, Michael E Sulewski, Chenguang Wang, Jiantao Song, Rupak Bhuyan, Jacob Sterling, Esther Clark, Wen-Chao Song, Joshua L Dunaief
PURPOSE: The complement system is involved in the pathogenesis of age-related macular degeneration (AMD). Because activated microglia are also associated with AMD, we studied the relationship between complement anaphylatoxin receptors and microglial recruitment. METHODS: We assessed the effect of anaphylatoxin C3a receptor (C3aR) and C5a receptor (C5aR) knockout (KO) on light damage-induced migration of microglia/macrophages into the mouse outer retina via immunofluorescence and real-time quantitative PCR...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28442497/an-in-silico-model-of-retinal-cholesterol-dynamics-rcd-model-insights-into-the-pathophysiology-of-dry-age-related-macular-degeneration
#17
Seyedeh Maryam Zekavat, James Lu, Cyrille Maugeais, Norman A Mazer
We developed an in-silico mathematical model of retinal cholesterol (Ch) dynamics (RCD) to quantify the physiological rate of Ch turnover in the rod outer segment (ROS), the lipoprotein transport mechanisms by which Ch enters and leaves the outer retina, and the rates of drusen growth and macrophage-mediated clearance in dry Age-Related Macular Degeneration (AMD). Based on existing experimental data and mechanistic hypotheses, we estimate the Ch turnover rate in the ROS to be 1-6 pg/mm2/min, dependent on the rate of Ch recycling in the outer retina, and find comparable rates for LDL receptor-mediated endocytosis of Ch by the retinal pigment epithelium (RPE), ABCA1-mediated Ch transport from the RPE to outer retina, ABCA1-mediated Ch efflux from the RPE to choroid, and the secretion of 70 nm ApoB-Ch particles from the RPE...
April 25, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28441076/a-novel-neuroprotective-small-molecule-for-glial-cell-derived-neurotrophic-factor-induction-and-photoreceptor-rescue
#18
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/28440413/different-distributions-of-m1-and-m2-macrophages-in-a-mouse-model-of-laser-induced-choroidal-neovascularization
#19
Yedi Zhou, Shigeo Yoshida, Yuki Kubo, Takeru Yoshimura, Yoshiyuki Kobayashi, Takahito Nakama, Muneo Yamaguchi, Keijiro Ishikawa, Yuji Oshima, Tatsuro Ishibashi
Choroidal neovascularization (CNV) is a serious complication of age‑related macular degeneration. The aim of the present study was to investigate the expression and distribution of M1 and M2 macrophages in a laser‑induced CNV adult mouse model. The mRNA expression levels of M1, M2 and pan macrophage markers, and macrophage‑associated angiogenic cytokines, were determined by reverse transcription‑quantitative polymerase chain reaction. Immunofluorescence studies were performed to determine the location of the macrophages...
June 2017: Molecular Medicine Reports
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
#20
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
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