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      Experimental Models of Glaucoma: A Powerful Translational Tool for the Future Development of New Therapies for Glaucoma in Humans—A Review of the Literature

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          Abstract

          Glaucoma is a common complex disease that leads to irreversible blindness worldwide. Even though preclinical studies showed that lowering intraocular pressure (IOP) could prevent retinal ganglion cells loss, clinical evidence suggests that lessening IOP does not prevent glaucoma progression in all patients. Glaucoma is also becoming more prevalent in the elderly population, showing that age is a recognized major risk factor. Indeed, recent findings suggest that age-related tissue alterations contribute to the development of glaucoma and have encouraged exploration for new treatment approaches. In this review, we provide information on the most frequently used experimental models of glaucoma and describe their advantages and limitations. Additionally, we describe diverse animal models of glaucoma that can be potentially used in translational medicine and aid an efficient shift to the clinic. Experimental animal models have helped to understand the mechanisms of formation and evacuation of aqueous humor, and the maintenance of homeostasis of intra-ocular pressure. However, the transfer of pre-clinical results obtained from animal studies into clinical trials may be difficult since the type of study does not only depend on the type of therapy to be performed, but also on a series of factors observed both in the experimental period and the period of transfer to clinical application. Conclusions: Knowing the exact characteristics of each glaucoma experimental model could help to diminish inconveniences related to the process of the translation of results into clinical application in humans.

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          Induced Pluripotent Stem Cells Meet Genome Editing.

          It is extremely rare for a single experiment to be so impactful and timely that it shapes and forecasts the experiments of the next decade. Here, we review how two such experiments-the generation of human induced pluripotent stem cells (iPSCs) and the development of CRISPR/Cas9 technology-have fundamentally reshaped our approach to biomedical research, stem cell biology, and human genetics. We will also highlight the previous knowledge that iPSC and CRISPR/Cas9 technologies were built on as this groundwork demonstrated the need for solutions and the benefits that these technologies provided and set the stage for their success.
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            The economic burden of major adult visual disorders in the United States.

            To estimate the societal economic burden and the governmental budgetary impact of the following visual disorders among US adults aged 40 years and older: visual impairment, blindness, refractive error, age-related macular degeneration, cataracts, diabetic retinopathy, and primary open-angle glaucoma. We estimated 3 components of economic burden: direct medical costs, other direct costs, and productivity losses. We used private insurance and Medicare claims data to estimate direct medical costs; epidemiologic evidence from multiple published sources to estimate other direct costs, such as nursing home costs; and data from the Survey of Income and Program Participation to estimate productivity losses. We used budgetary documents and our direct medical and other direct cost estimates to approximate the governmental budgetary impact. We estimated that the annual total financial burden of major adult visual disorders is $35.4 billion ($16.2 billion in direct medical costs, $11.1 billion in other direct costs, and $8 billion in productivity losses) and that the annual governmental budgetary impact is $13.7 billion. Major visual disorders among Americans older than 40 years result in substantial economic costs for the US economy. Well-designed public health programs may have the ability to reduce this burden in the future.
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              Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development.

              To rapidly identify genes required for early vertebrate development, we are carrying out a large-scale, insertional mutagenesis screen in zebrafish, using mouse retroviral vectors as the mutagen. We will obtain mutations in 450 to 500 different genes--roughly 20% of the genes that can be mutated to produce a visible embryonic phenotype in this species--and will clone the majority of the mutated alleles. So far, we have isolated more than 500 insertional mutants. Here we describe the first 75 insertional mutants for which the disrupted genes have been identified. In agreement with chemical mutagenesis screens, approximately one-third of the mutants have developmental defects that affect primarily one or a small number of organs, body shape or swimming behavior; the rest of the mutants show more widespread or pleiotropic abnormalities. Many of the genes we identified have not been previously assigned a biological role in vivo. Roughly 20% of the mutants result from lesions in genes for which the biochemical and cellular function of the proteins they encode cannot be deduced with confidence, if at all, from their predicted amino-acid sequences. All of the genes have either orthologs or clearly related genes in human. These results provide an unbiased view of the genetic construction kit for a vertebrate embryo, reveal the diversity of genes required for vertebrate development and suggest that hundreds of genes of unknown biochemical function essential for vertebrate development have yet to be identified.
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                Author and article information

                Journal
                Medicina (Kaunas)
                medicina
                Medicina
                MDPI
                1010-660X
                1648-9144
                17 June 2019
                June 2019
                : 55
                : 6
                : 280
                Affiliations
                [1 ]Doctorado en Ciencias Biomédicas y Biológicas, Facultad de Ciencias Naturales y Matemáticas, Universidad del Rosario, Bogotá,11121, Colombia; evangelho.karine@ 123456gmail.com
                [2 ]Neuroscience Research Group (NeurUROS), Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, 11121, Colombia; mastronardic@ 123456hotmail.com
                Author notes
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-1340-3266
                https://orcid.org/0000-0003-0684-1989
                Article
                medicina-55-00280
                10.3390/medicina55060280
                6630440
                31212881
                51d8ef68-6c31-40ca-981e-79926e5a453e
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 January 2019
                : 04 June 2019
                Categories
                Review

                glaucoma,experimental models,therapy,animals,aging,translational ophthalmology

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