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      Novel stem cell and gene therapy in diabetic retinopathy, age related macular degeneration, and retinitis pigmentosa

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          Abstract

          Degenerative retinal disease leads to significant visual morbidity worldwide. Diabetic retinopathy and macular degeneration are leading causes of blindness in the developed world. While current therapies for these diseases slow disease progression, stem cell and gene therapy may also reverse the effects of these, and other, degenerative retinal conditions. Novel therapies being investigated include the use of various types of stem cells in the regeneration of atrophic or damaged retinal tissue, the prolonged administration of neurotrophic factors and/or drug delivery, immunomodulation, as well as the replacement of mutant genes, and immunomodulation through viral vector delivery. This review will update the reader on aspects of stem cell and gene therapy in diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa and other less common inherited retinal dystrophies. These therapies include the use of adeno-associated viral vector-based therapies for treatment of various types of retinitis pigmentosa and dry age-related macular degeneration. Other potential therapies reviewed include the use of mesenchymal stem cells in local immunomodulation, and the use of stem cells in generating structures like three-dimensional retinal sheets for transplantation into degenerative retinas. Finally, aspects of stem cell and gene therapy in diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and other less common inherited retinal dystrophies will be reviewed.

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          Causes and prevalence of visual impairment among adults in the United States.

          Nathan Congdon, Benita J O'Colmain, Caroline C. W. Klaver … (2004)
          To estimate the cause-specific prevalence and distribution of blindness and low vision in the United States by age, race/ethnicity, and gender, and to estimate the change in these prevalence figures over the next 20 years. Summary prevalence estimates of blindness (both according to the US definition of < or =6/60 [< or =20/200] best-corrected visual acuity in the better-seeing eye and the World Health Organization standard of < 6/120 [< 20/400]) and low vision (< 6/12 [< 20/40] best-corrected vision in the better-seeing eye) were prepared separately for black, Hispanic, and white persons in 5-year age intervals starting at 40 years. The estimated prevalences were based on recent population-based studies in the United States, Australia, and Europe. These estimates were applied to 2000 US Census data, and to projected US population figures for 2020, to estimate the number of Americans with visual impairment. Cause-specific prevalences of blindness and low vision were also estimated for the different racial/ethnic groups. Based on demographics from the 2000 US Census, an estimated 937 000 (0.78%) Americans older than 40 years were blind (US definition). An additional 2.4 million Americans (1.98%) had low vision. The leading cause of blindness among white persons was age-related macular degeneration (54.4% of the cases), while among black persons, cataract and glaucoma accounted for more than 60% of blindness. Cataract was the leading cause of low vision, responsible for approximately 50% of bilateral vision worse than 6/12 (20/40) among white, black, and Hispanic persons. The number of blind persons in the US is projected to increase by 70% to 1.6 million by 2020, with a similar rise projected for low vision. Blindness or low vision affects approximately 1 in 28 Americans older than 40 years. The specific causes of visual impairment, and especially blindness, vary greatly by race/ethnicity. The prevalence of visual disabilities will increase markedly during the next 20 years, owing largely to the aging of the US population.
          Article 0 comments Cited 543 times – based on 0 reviews     Review now
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            Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies

            Steven D Schwartz, Carl Regillo, Byron L Lam … (2015)
            The Lancet, 385(9967), 509-516
            Article 0 comments Cited 443 times – based on 0 reviews     Review now
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              A central role for inflammation in the pathogenesis of diabetic retinopathy.

              Antonia Joussen, Vassiliki Poulaki, Minh Ly Le … (2004)
              Diabetic retinopathy is a leading cause of adult vision loss and blindness. Much of the retinal damage that characterizes the disease results from retinal vascular leakage and nonperfusion. Diabetic retinal vascular leakage, capillary nonperfusion, and endothelial cell damage are temporary and spatially associated with retinal leukocyte stasis in early experimental diabetes. Retinal leukostasis increases within days of developing diabetes and correlates with the increased expression of retinal intercellular adhesion molecule-1 (ICAM-1) and CD18. Mice deficient in the genes encoding for the leukocyte adhesion molecules CD18 and ICAM-1 were studied in two models of diabetic retinopathy with respect to the long-term development of retinal vascular lesions. CD18-/- and ICAM-1-/- mice demonstrate significantly fewer adherent leukocytes in the retinal vasculature at 11 and 15 months after induction of diabetes with STZ. This condition is associated with fewer damaged endothelial cells and lesser vascular leakage. Galactosemia of up to 24 months causes pericyte and endothelial cell loss and formation of acellular capillaries. These changes are significantly reduced in CD18- and ICAM-1-deficient mice. Basement membrane thickening of the retinal vessels is increased in long-term galactosemic animals independent of the genetic strain. Here we show that chronic, low-grade subclinical inflammation is responsible for many of the signature vascular lesions of diabetic retinopathy. These data highlight the central and causal role of adherent leukocytes in the pathogenesis of diabetic retinopathy. They also underscore the potential utility of anti-inflammatory treatment in diabetic retinopathy.
              Article 0 comments Cited 347 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Parker E. Ludwig: parkerludwig@creighton.edu
                S. Caleb Freeman: stevenfreeman@creighton.edu
                Adam C. Janot: acjanot1@gmail.com
                Journal
                Journal ID (nlm-ta): Int J Retina Vitreous
                Journal ID (iso-abbrev): Int J Retina Vitreous
                Title: International Journal of Retina and Vitreous
                Publisher: BioMed Central (London )
                ISSN (Electronic): 2056-9920
                Publication date (Electronic): 13 February 2019
                Publication date PMC-release: 13 February 2019
                Publication date Collection: 2019
                Volume: 5
                Electronic Location Identifier: 7
                Affiliations
                [1 ]ISNI 0000 0004 1936 8876, GRID grid.254748.8, Creighton University School of Medicine, ; 2500 California Plaza, Omaha, NE 68178 USA
                [2 ]Vitreoretinal Institute, 7698 Goodwood Blvd, Baton Rouge, LA 70806 USA
                [3 ]ISNI 0000 0000 8954 1233, GRID grid.279863.1, Department of Ophthalmology, , Louisiana State University Health Sciences Center, ; New Orleans, LA USA
                Article
                Publisher ID: 158
                DOI: 10.1186/s40942-019-0158-y
                PMC ID: 6373096
                PubMed ID: 30805203
                SO-VID: 7462c12e-1e8b-4b0b-8652-c601e1cf9adb
                Copyright © © The Author(s) 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 9 October 2018
                Date accepted : 28 January 2019
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

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