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AMD animal

Xincheng Yao, Taeyoon Son, Tae-Hoon Kim, Yiming Lu
Retinal photoreceptors are the primary target of age-related macular degeneration (AMD) which is the leading cause of severe vision loss and legal blindness. An objective method for functional assessment of photoreceptor physiology can benefit early detection and better treatment evaluation of AMD and other eye diseases that are known to cause photoreceptor dysfunctions. This article summarizes in vitro study of IOS mechanisms and in vivo demonstration of IOS imaging of intact animals. Further development of the functional IOS imaging may provide a revolutionary solution to achieve objective assessment of human photoreceptors...
November 27, 2018: Experimental Biology and Medicine
Karis Little, Jacey H Ma, Nan Yang, Mei Chen, Heping Xu
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in developed countries. Neovascular AMD (nAMD) accounts for 90% of AMD-related vision loss. Although intravitreal injection of VEGF inhibitors can improve vision in nAMD, approximately 1/3 of patients do not benefit from the therapy due to macular fibrosis. The molecular mechanism underlying the transition of the neovascular lesion to a fibrovascular phenotype remains unknown. Here we discussed the clinical features and risk factors of macular fibrosis secondary to nAMD...
November 22, 2018: EBioMedicine
Sylvia J Gasparini, Sílvia Llonch, Oliver Borsch, Marius Ader
The mammalian retina displays no intrinsic regenerative capacities, therefore retinal degenerative diseases such as age-related macular degeneration (AMD) or retinitis pigmentosa (RP) result in a permanent loss of the light-sensing photoreceptor cells. The degeneration of photoreceptors leads to vision impairment and, in later stages, complete blindness. Several therapeutic strategies have been developed to slow down or prevent further retinal degeneration, however a definitive cure i.e. replacement of the lost photoreceptors, has not yet been established...
November 13, 2018: Progress in Retinal and Eye Research
Zi-Bing Jin, Mei-Ling Gao, Wen-Li Deng, Kun-Chao Wu, Sunao Sugita, Michiko Mandai, Masayo Takahashi
Cell replacement therapy is a promising treatment for irreversible retinal cell death in diverse diseases, such as age-related macular degeneration (AMD), Stargardt's disease, retinitis pigmentosa (RP) and glaucoma. These diseases are all characterized by the degeneration of one or two retinal cell types that cannot regenerate spontaneously in humans. Aberrant retinal pigment epithelial (RPE) cells can be observed through optical coherence tomography (OCT) in AMD patients. In RP patients, the morphological and functional abnormalities of RPE and photoreceptor layers are caused by a genetic abnormality...
November 9, 2018: Progress in Retinal and Eye Research
Christine A Curcio
AMD is a major cause of legal blindness in older adults approachable through multidisciplinary research involving human tissues and patients. AMD is a vascular-metabolic-inflammatory disease, in which two sets of extracellular deposits, soft drusen/basal linear deposit (BLinD) and subretinal drusenoid deposit (SDD), confer risk for end-stages of atrophy and neovascularization. Understanding how deposits form can lead to insights for new preventions and therapy. The topographic correspondence of BLinD and SDD with cones and rods, respectively, suggest newly realized exchange pathways among outer retinal cells and across Bruch's membrane and the subretinal space, in service of highly evolved, eye-specific physiology...
March 20, 2018: Investigative Ophthalmology & Visual Science
Zeljka Smit-McBride, Johnny Nguyen, Garrett W Elliott, Zhe Wang, Ryan A McBride, Anthony T Nguyen, Sharon L Oltjen, Glenn Yiu, Sara M Thomasy, Kent E Pinkerton, Eugene S Lee, David Cunefare, Sina Farsiu, Lawrence S Morse
Purpose: To identify changes induced by environmental tobacco smoke (ETS) in circulatory microRNA (miRNA) in plasma and ocular fluids of the Rhesus macaque and compare these changes to normal age-related changes. Tobacco smoke has been identified as the leading environmental risk factor for age-related macular degeneration (AMD). Methods: All Rhesus macaques were housed at the California National Primate Research Center (CNPRC), University of California, Davis. Four groups of animals were used: Group 1 (1-3 years old), Group 2 (19-28 years old), Group 3 (10-16 years old), and Group 4 (middle aged, 9-14 years old)...
2018: Molecular Vision
Nataliya G Kolosova, Oyuna S Kozhevnikova, Darya V Telegina, Anzhela Zh Fursova, Natalia A Stefanova, Natalia A Muraleva, Franco Venanzi, Michael Y Sherman, Sergey I Kolesnikov, Albert A Sufianov, Vladimir L Gabai, Alexander M Shneider
P62/SQSTM1, a multi-domain protein that regulates inflammation, apoptosis, and autophagy, has been linked to age-related pathologies. For example, previously we demonstrated that administration of p62/SQSTM1-encoding plasmid reduced chronic inflammation and alleviated osteoporosis and metabolic syndrome in animal models. Herein, we built upon these findings to investigate effect of the p62-encoding plasmid on an age-related macular degeneration (AMD), a progressive neurodegenerative ocular disease, using spontaneous retinopathy in senescence-accelerated OXYS rats as a model...
August 28, 2018: Aging
Rehan M Hussain, Thomas A Ciulla, Audina M Berrocal, Ninel Z Gregori, Harry W Flynn, Byron L Lam
Stargardt macular dystrophy (STGD1) is a hereditary retinal degeneration that lacks effective treatment options. Gene therapy, stem cell therapy, and pharmacotherapy with visual cycle modulators (VCMs) and complement inhibitors are discussed as potential treatments. Areas covered: Investigational therapies for STGD1 aim to reduce toxic bisretinoids and lipofuscin in the retina and retinal pigment epithelium (RPE). These agents include C20-D3-vitamin A (ALK-001), isotretinoin, VM200, emixustat, and A1120. Avacincaptad pegol is a C5 complement inhibitor that may reduce inflammation-related RPE damage...
October 2018: Expert Opinion on Biological Therapy
Akane Kashimura, Kouji Tanaka, Hiroko Sato, Hidefumi Kaji, Masaharu Tanaka
To evaluate the usefulness of imaging mass spectrometry (IMS) technology for assessing drug toxicity, we analyzed animal tissues in an amiodarone (AMD)-induced phospholipidosis model by IMS and confirmed the relationship between the distribution of AMD, its metabolites, and representative phospholipids (phosphatidylcholine, PC) and histological changes. AMD was administered to rats for 7 days at 150 mg/kg/day. The lung, spleen, and mesenteric lymph node were histologically examined and analyzed using IMS. The detection intensities of AMD, its metabolites, and typical PCs were higher in regions infiltrated by foamy macrophages compared with normal areas...
July 2018: Journal of Toxicologic Pathology
Yizhe Cui, Qiuju Wang, Rui Sun, Li Guo, Mengzhu Wang, Junfeng Jia, Chuang Xu, Rui Wu
BACKGROUND: Astragalus membranaceus (Fisch.) Bunge is one of the most widely used traditional Chinese herbal medicines. It is used as immune stimulant, tonic, antioxidant, hepatoprotectant, diuretic, antidiabetic, anticancer, and expectorant. The purpose of the study was to investigate the curative effects of the decoction obtained from Astragalus membranaceus root in intestinal mucosal injury induced by LPS in mice. An LPS-induced intestinal mucosal injury mice model was applied in the study...
August 3, 2018: BMC Complementary and Alternative Medicine
David A Copland, Sofia Theodoropoulou, Jian Liu, Andrew D Dick
Despite strong genetic associations, compelling human histological data and numerous hypotheses generated with supportive animal data, the mechanisms of inflammation or inflammatory control of cell health during progression of age-related macular degeneration arguably remain elusive. This perspective delivers a view that maintaining tissue health requires active immune cellular and tissue pathways, but when responses are perturbed or exaggerated, chronic inflammation is destructive. There are potential pathways and processes to enable understanding and determine how potential causative factors including altered cellular metabolism, senescence, oxidative stress disrupt tissue homeostasis are engaged...
March 20, 2018: Investigative Ophthalmology & Visual Science
Naoko A Chapman, Robert J Jacobs, Andrea J Braakhuis
A systematic literature review was conducted to evaluate the role of diet and food intake in age-related macular degeneration (AMD). Eighteen high-quality studies were identified. Adherence to a Mediterranean diet had decreased risk of AMD progression. An Oriental diet pattern had decreased association with AMD prevalence, whereas a Western diet pattern had increased association with AMD prevalence. High consumption of vegetables rich in carotenoids and fatty fish containing omega-3 fatty acids was beneficial for those at risk of AMD...
June 21, 2018: Clinical & Experimental Ophthalmology
Mikhail Linetsky, Karina S Bondelid, Sofiya Losovskiy, Vadym Gabyak, Mario J Rullo, Thomas I Stiadle, Vasu Munjapara, Priyali Saxena, Duoming Ma, Yu-Shiuan Cheng, Andrew M Howes, Emeka Udeigwe, Robert G Salomon
We previously discovered that oxidative cleavage of docosahexaenoate (DHA), which is especially abundant in the retinal photoreceptor rod outer segments and retinal pigmented endothelial (RPE) cells, generates 4-hydroxy-7-oxo-5-heptenoate (HOHA) lactone, and that HOHA lactone can enter RPE cells that metabolize it through conjugation with glutathione (GSH). The consequent depletion of GSH results in oxidative stress. We now find that HOHA lactone induces upregulation of the antioxidant transcription factor Nrf2 in ARPE-19 cells...
August 20, 2018: Chemical Research in Toxicology
Yuki Muraoka, Yuto Iida, Hanako O Ikeda, Sachiko Iwai, Masayuki Hata, Takeshi Iwata, Mao Nakayama, Nobuhiro Shimozawa, Yuko Katakai, Akira Kakizuka, Nagahisa Yoshimura, Akitaka Tsujikawa
Age-related macular degeneration (AMD) is a leading cause of blindness among elderly people. The appearance of drusen is a clinical manifestation and a harbinger of both exudative and atrophic AMD. Recently, antibody-based medicines have been used to treat the exudative type. However, they do not restore good vision in patients. Moreover, no effective treatment is available for atrophic AMD. We have created small chemicals (Kyoto University Substances; KUSs) that act as ATP regulators inside cells. In the present study, we examined the in vivo efficacy of KUS121 in C-C chemokine receptor type 2-deficient mice, a mouse model of AMD...
May 2018: Heliyon
Yang Lyu, Wen-Qin Xu, Li-Juan Sun, Xiao-Yan Pan, Jian Zhang, Yu-Sheng Wang
AIM: To investigate the roles of integrins in choroidal neovascularization (CNV) and their associations with the stromal cell-derived factor-1 (SDF-1)/CXCR4 axis. METHODS: CNV lesions were induced in mice using laser photocoagulation. After CNV induction, all animals were randomly assigned to: control, SDF-1, SDF-1+age-related macular degeneration (AMD) 3100 (CXCR4 inhibitor), and SDF-1+ATN161 (integrin α5β1 inhibitor) groups; their effects on CNV progression were observed using hematoxylin eosin (HE) staining, fundus fluorescein angiography (FFA) grading and optical coherence tomography (OCT), and their effects on CXCR4/integrin α5 expression were evaluated using Western blot and double immunofluorescence staining...
2018: International Journal of Ophthalmology
Thierry Menguy, Anne Briaux, Elisabeth Jeunesse, Jérôme Giustiniani, Alexandre Calcei, Thierry Guyon, Jacques Mizrahi, Hélène Haegel, Vanessa Duong, Vincent Soler, Pierre Brousset, Armand Bensussan, Isabelle Raymond Letron, Philippe Le Bouteiller
Purpose: To assess the efficacy of the murine first-in-class CL1-R2 monoclonal antibody (mAb) targeting human CD160 (alone or in combination with bevacizumab) by using the rabbit corneal neovascularization (CNV) model, and determine the safety and efficacy of ELB01101, a novel CL1-R2-derived humanized IgG4 mAb, in a monkey model of choroidal neovascularization (ChNV). Methods: Comparison of effect of CL1-R2, bevacizumab, or aflibercept or IgG1 (control) injections in early and late treatment schemes on evolution of VEGF- or FGF2-induced rabbit CNV was performed...
June 1, 2018: Investigative Ophthalmology & Visual Science
Gauthier Aldebert, Jean-Luc Faillie, Dominique Hillaire-Buys, Thibault Mura, Isabelle Carrière, Cécile Delcourt, Catherine Creuzot-Garcher, Max Villain, Vincent Daien
Importance: Amyloid-β is a major component of retinal drusen, the primary lesions of age-related macular degeneration (AMD), and autopsy and animal models suggested that anticholinergic drug (ACD) use increased brain amyloid-β deposition. Objective: To investigate the association between exposure to ACDs and late AMD (features of neovascular AMD or geographic atrophy of the retinal pigment epithelium in at least 1 eye). Design, Setting and Participants: A multicenter case-control study in 4 French ophthalmologic centers comprising 200 cases with late AMD and 200 controls enrolled from July 2016 to June 2017...
July 1, 2018: JAMA Ophthalmology
Laura E Downie, Ljoudmila Busija, Peter R Keller
BACKGROUND: An intraocular lens (IOL) is a synthetic lens that is surgically implanted within the eye following removal of the crystalline lens, during cataract surgery. While all modern IOLs attenuate the transmission of ultra-violet (UV) light, some IOLs, called blue-blocking or blue-light filtering IOLs, also reduce short-wavelength visible light transmission. The rationale for blue-light filtering IOLs derives primarily from cell culture and animal studies, which suggest that short-wavelength visible light can induce retinal photoxicity...
May 22, 2018: Cochrane Database of Systematic Reviews
Margaret D Weinroth, H Morgan Scott, Bo Norby, Guy H Loneragan, Noelle R Noyes, Pablo Rovira, Enrique Doster, Xiang Yang, Dale R Woerner, Paul S Morley, Keith E Belk
Treatment of food-producing animals with antimicrobial drugs (AMD) is controversial because of concerns regarding promotion of antimicrobial resistance (AMR). To investigate this concern, resistance genes in metagenomic bovine fecal samples during a clinical trial were analyzed to assess the impacts of treatment on beef feedlot cattle resistomes. Four groups of cattle were exposed, using a 2-by-2 factorial design, to different regimens of antimicrobial treatment. Injections of ceftiofur crystalline-free acid (a third-generation cephalosporin) were used to treat all cattle in treatment pens or only a single animal, and either chlortetracycline was included in the feed of all cattle in a pen or the feed was untreated...
July 1, 2018: Applied and Environmental Microbiology
Vladimir Khristov, Arvydas Maminishkis, Juan Amaral, Aaron Rising, Kapil Bharti, Sheldon Miller
Previous work suggests that replacing diseased Retinal Pigment Epithelium (RPE) with a healthy autologous RPE sheet can provide vision rescue for AMD patients. We differentiated iPSCs into RPE using a directed differentiation protocol. RPE cells at the immature RPE stage were purified and seeded onto either electrospun poly(lactic-co-glycolic acid) (PLGA) scaffolds or non-biodegradable polyester cell culture inserts and compared the two tissues. In vitro, PLGA and polyester substrates produced functionally similar results...
2018: Advances in Experimental Medicine and Biology
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