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Review Series

The Eye

Series edited by Lois E.H. Smith

The mammalian eye is a markedly complex organ, and disruption of normal cell physiology at any of a number of levels may result in a devastating loss of vision. In recent years, ophthalmology research has advanced our understanding of fields as diverse as development, aging, immunology, and cancer. The articles in this series review this progress and highlight how the unique biology of the eye has allowed rapid advances in the areas of gene therapy and stem cell research.

Articles in series

An eye for discovery
Andreas Stahl, Lois E.H. Smith
Andreas Stahl, Lois E.H. Smith
Published September 1, 2010
Citation Information: J Clin Invest. 2010;120(9):3008-3011. https://doi.org/10.1172/JCI44158.
View: Text | PDF

An eye for discovery

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Abstract

Vision research has often led to significant advances in our understanding of biology. There has also been particular success in translating basic research in the eye into breakthrough clinical therapies that mark important milestones for ophthalmology and also for medical research. Anti-VEGF therapy for age-related macular degeneration was named as one of the top ten science advancements of the year 2006. Only two years later, successful transfer of the RPE65 gene into retinal pigment epithelium of patients with Leber congenital amaurosis was noted as one of the most important clinical applications of gene therapy. The articles in this Review series outline current developments in vision research and highlight its continued importance in ophthalmology and medicine.

Authors

Andreas Stahl, Lois E.H. Smith

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Stemming vision loss with stem cells
Valentina Marchetti, … , David F. Friedlander, Martin Friedlander
Valentina Marchetti, … , David F. Friedlander, Martin Friedlander
Published September 1, 2010
Citation Information: J Clin Invest. 2010;120(9):3012-3021. https://doi.org/10.1172/JCI42951.
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Stemming vision loss with stem cells

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Abstract

Dramatic advances in the field of stem cell research have raised the possibility of using these cells to treat a variety of diseases. The eye is an excellent target organ for such cell-based therapeutics due to its ready accessibility, the prevalence of vasculo- and neurodegenerative diseases affecting vision, and the availability of animal models to demonstrate proof of concept. In fact, stem cell therapies have already been applied to the treatment of disease affecting the ocular surface, leading to preservation of vision. Diseases in the back of the eye, such as macular degeneration, diabetic retinopathy, and inherited retinal degenerations, present greater challenges, but rapidly emerging stem cell technologies hold the promise of autologous grafts to stabilize vision loss through cellular replacement or paracrine rescue effects.

Authors

Valentina Marchetti, Tim U. Krohne, David F. Friedlander, Martin Friedlander

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Retinopathy of prematurity: understanding ischemic retinal vasculopathies at an extreme of life
Przemyslaw Sapieha, … , Pierre Lachapelle, Sylvain Chemtob
Przemyslaw Sapieha, … , Pierre Lachapelle, Sylvain Chemtob
Published September 1, 2010
Citation Information: J Clin Invest. 2010;120(9):3022-3032. https://doi.org/10.1172/JCI42142.
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Retinopathy of prematurity: understanding ischemic retinal vasculopathies at an extreme of life

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Abstract

Retinopathy of prematurity (ROP) is a major complication of preterm birth. It encompasses a spectrum of pathologies that affect vision, from mild disease that resolves spontaneously to severe disease that causes retinal detachment and subsequent blindness. The pathologies are characterized by an arrest in normal retinal vascular development associated with microvascular degeneration. The resulting ischemia and retinal hypoxia lead to excessive abnormal compensatory blood vessel growth. However, this neovascularization can lead to fibrous scar formation and culminate in retinal detachment. Present therapeutic modalities to limit the adverse consequences of aberrant neovascularization are invasive and/or tissue-destructive. In this Review, we discuss current concepts on retinal microvascular degeneration, neovascularization, and available treatments, as well as present future perspectives toward more profound elucidation of the pathogenesis of ROP.

Authors

Przemyslaw Sapieha, Jean-Sebastien Joyal, José Carlos Rivera, Elsa Kermorvant-Duchemin, Florian Sennlaub, Pierre Hardy, Pierre Lachapelle, Sylvain Chemtob

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Therapeutic targets in age-related macular disease
Alan C. Bird
Alan C. Bird
Published September 1, 2010
Citation Information: J Clin Invest. 2010;120(9):3033-3041. https://doi.org/10.1172/JCI42437.
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Therapeutic targets in age-related macular disease

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Abstract

Age-related macular disease (AMD) accounts for more than 50% of blind registration in Western society. Patients with AMD are classified as having early disease, in which visual function is well preserved, or late disease, in which central vision is lost. Until recently, there was no therapy available by which the course of the disorder could be modified. Now, the most common form of late-stage AMD — choroidal neovascularization — responds to treatment with anti-VEGF therapies; although visual loss is modified in a portion of these cases, no therapeutic approach exists that alters the evolution from early to late disease. However, as discussed in this Review, research over the last few years has demonstrated several features of AMD that are likely to be amenable to treatment. Potential targets for treatment are described, and possible therapeutic approaches are discussed.

Authors

Alan C. Bird

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Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies
Anneke I. den Hollander, … , Jean Bennett, Frans P.M. Cremers
Anneke I. den Hollander, … , Jean Bennett, Frans P.M. Cremers
Published September 1, 2010
Citation Information: J Clin Invest. 2010;120(9):3042-3053. https://doi.org/10.1172/JCI42258.
View: Text | PDF | Corrigendum

Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies

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Abstract

Nonsyndromic recessive retinal dystrophies cause severe visual impairment due to the death of photoreceptor and retinal pigment epithelium cells. These diseases until recently have been considered to be incurable. Molecular genetic studies in the last two decades have revealed the underlying molecular causes in approximately two-thirds of patients. The mammalian eye has been at the forefront of therapeutic trials based on gene augmentation in humans with an early-onset nonsyndromic recessive retinal dystrophy due to mutations in the retinal pigment epithelium–specific protein 65kDa (RPE65) gene. Tremendous challenges still lie ahead to extrapolate these studies to other retinal disease–causing genes, as human gene augmentation studies require testing in animal models for each individual gene and sufficiently large patient cohorts for clinical trials remain to be identified through cost-effective mutation screening protocols.

Authors

Anneke I. den Hollander, Aaron Black, Jean Bennett, Frans P.M. Cremers

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How cortical neurons help us see: visual recognition in the human brain
Julie Blumberg, Gabriel Kreiman
Julie Blumberg, Gabriel Kreiman
Published September 1, 2010
Citation Information: J Clin Invest. 2010;120(9):3054-3063. https://doi.org/10.1172/JCI42161.
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How cortical neurons help us see: visual recognition in the human brain

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Abstract

Through a series of complex transformations, the pixel-like input to the retina is converted into rich visual perceptions that constitute an integral part of visual recognition. Multiple visual problems arise due to damage or developmental abnormalities in the cortex of the brain. Here, we provide an overview of how visual information is processed along the ventral visual cortex in the human brain. We discuss how neurophysiological recordings in macaque monkeys and in humans can help us understand the computations performed by visual cortex.

Authors

Julie Blumberg, Gabriel Kreiman

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Glaucoma: genes, phenotypes, and new directions for therapy
Bao Jian Fan, Janey L. Wiggs
Bao Jian Fan, Janey L. Wiggs
Published September 1, 2010
Citation Information: J Clin Invest. 2010;120(9):3064-3072. https://doi.org/10.1172/JCI43085.
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Glaucoma: genes, phenotypes, and new directions for therapy

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Abstract

Glaucoma, a leading cause of blindness worldwide, is characterized by progressive optic nerve damage, usually associated with intraocular pressure. Although the clinical progression of the disease is well defined, the molecular events responsible for glaucoma are currently poorly understood and current therapeutic strategies are not curative. This review summarizes the human genetics and genomic approaches that have shed light on the complex inheritance of glaucoma genes and the potential for gene-based and cellular therapies that this research makes possible.

Authors

Bao Jian Fan, Janey L. Wiggs

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A look at autoimmunity and inflammation in the eye
Rachel R. Caspi
Rachel R. Caspi
Published September 1, 2010
Citation Information: J Clin Invest. 2010;120(9):3073-3083. https://doi.org/10.1172/JCI42440.
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A look at autoimmunity and inflammation in the eye

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Abstract

Autoimmune and inflammatory uveitis are a group of potentially blinding intraocular inflammatory diseases that arise without a known infectious trigger and are often associated with immunological responses to unique retinal proteins. In the United States, about 10% of the cases of severe visual handicap are attributed to this group of disorders. As I discuss here, experimental models of ocular autoimmunity targeting retinal proteins have brought about a better understanding of the basic immunological mechanisms involved in the pathogenesis of uveitis and are serving as templates for the development of novel therapies.

Authors

Rachel R. Caspi

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