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Gene therapy for red–green colour blindness in adult primates | Nature

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For example, it might be expected that gene therapy in adults with congenital vision disorders would be impossible. But experiments in adult spider monkeys who are normally red–green colour blind show that it is possible to add a third photopigment (human opsin) into some of their retinal cells by gene therapy. The monkeys acquire a new dimension of colour vision as a result. Not only does this suggest a possible therapy for a common congenital visual defect in humans (clinical trials are now under way), but also it demonstrates the extreme neuroplasticity of visual processing and points to possible routes by which trichromatic vision evolved. Red–green colour blindness is the most common single locus genetic disorder. Gene therapy is now used in adult monkeys, colour blind since birth, to provide the receptoral basis for trichromatic colour vision. Despite the expectation from classic visual deprivation experiments that neural connections established during development are incapable of processing an input not present from birth, treated monkeys displayed trichromatic colour vision behaviour. Red–green colour blindness, which results from the absence of either the long- (L) or the middle- (M) wavelength-sensitive visual photopigments, is the most common single locus genetic disorder. Here we explore the possibility of curing colour blindness using gene therapy in experiments on adult monkeys that had been colour blind since birth. A third type of cone pigment was added to dichromatic retinas, providing the receptoral basis for trichromatic colour vision. This opened a new avenue to explore the requirements for establishing the neural circuits for a new dimension of colour sensation. Classic visual deprivation experiments1 have led to the expectation that neural connections established during development would not appropriately process an input that was not present from birth. Therefore, it was believed that the treatment of congenital vision disorders would be ineffective unless administered to the very young. However, here we show that the addition of a third opsin in adult red–green colour-deficient primates was sufficient to produce trichromatic colour vision behaviour. Thus, trichromacy can arise from a single addition of a third cone class and it does not require an early developmental process. 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All rights reserved"> <meta name="dc.rights" content="2009 Macmillan Publishers Limited. All rights reserved"> <meta name="dc.rightsAgent" content="journalpermissions@springernature.com"> <meta name="dc.description" content="It is often assumed that critical periods exist for the development of vision and other neural capabilities and that they end prior to adolescence. For example, it might be expected that gene therapy in adults with congenital vision disorders would be impossible. But experiments in adult spider monkeys who are normally red–green colour blind show that it is possible to add a third photopigment (human opsin) into some of their retinal cells by gene therapy. The monkeys acquire a new dimension of colour vision as a result. Not only does this suggest a possible therapy for a common congenital visual defect in humans (clinical trials are now under way), but also it demonstrates the extreme neuroplasticity of visual processing and points to possible routes by which trichromatic vision evolved. Red–green colour blindness is the most common single locus genetic disorder. Gene therapy is now used in adult monkeys, colour blind since birth, to provide the receptoral basis for trichromatic colour vision. Despite the expectation from classic visual deprivation experiments that neural connections established during development are incapable of processing an input not present from birth, treated monkeys displayed trichromatic colour vision behaviour. Red–green colour blindness, which results from the absence of either the long- (L) or the middle- (M) wavelength-sensitive visual photopigments, is the most common single locus genetic disorder. Here we explore the possibility of curing colour blindness using gene therapy in experiments on adult monkeys that had been colour blind since birth. A third type of cone pigment was added to dichromatic retinas, providing the receptoral basis for trichromatic colour vision. This opened a new avenue to explore the requirements for establishing the neural circuits for a new dimension of colour sensation. Classic visual deprivation experiments1 have led to the expectation that neural connections established during development would not appropriately process an input that was not present from birth. Therefore, it was believed that the treatment of congenital vision disorders would be ineffective unless administered to the very young. However, here we show that the addition of a third opsin in adult red–green colour-deficient primates was sufficient to produce trichromatic colour vision behaviour. 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For example, it might be expected that gene therapy in adults with congenital vision disorders would be impossible. But experiments in adult spider monkeys who are normally red–green colour blind show that it is possible to add a third photopigment (human opsin) into some of their retinal cells by gene therapy. The monkeys acquire a new dimension of colour vision as a result. Not only does this suggest a possible therapy for a common congenital visual defect in humans (clinical trials are now under way), but also it demonstrates the extreme neuroplasticity of visual processing and points to possible routes by which trichromatic vision evolved. Red–green colour blindness is the most common single locus genetic disorder. Gene therapy is now used in adult monkeys, colour blind since birth, to provide the receptoral basis for trichromatic colour vision. Despite the expectation from classic visual deprivation experiments that neural connections established during development are incapable of processing an input not present from birth, treated monkeys displayed trichromatic colour vision behaviour. Red–green colour blindness, which results from the absence of either the long- (L) or the middle- (M) wavelength-sensitive visual photopigments, is the most common single locus genetic disorder. Here we explore the possibility of curing colour blindness using gene therapy in experiments on adult monkeys that had been colour blind since birth. A third type of cone pigment was added to dichromatic retinas, providing the receptoral basis for trichromatic colour vision. This opened a new avenue to explore the requirements for establishing the neural circuits for a new dimension of colour sensation. Classic visual deprivation experiments1 have led to the expectation that neural connections established during development would not appropriately process an input that was not present from birth. Therefore, it was believed that the treatment of congenital vision disorders would be ineffective unless administered to the very young. However, here we show that the addition of a third opsin in adult red–green colour-deficient primates was sufficient to produce trichromatic colour vision behaviour. Thus, trichromacy can arise from a single addition of a third cone class and it does not require an early developmental process. 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data-test="article-category">Letter</li> <li class="c-article-identifiers__item">Published: <time datetime="2009-09-16">16 September 2009</time></li> </ul> <h1 class="c-article-title" data-test="article-title" data-article-title="">Gene therapy for red–green colour blindness in adult primates</h1> <ul class="c-article-author-list c-article-author-list--short" data-test="authors-list" data-component-authors-activator="authors-list"> <li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#auth-Katherine-Mancuso-Aff1" data-author-popup="auth-Katherine-Mancuso-Aff1" data-author-search="Mancuso, Katherine">Katherine Mancuso</a><sup class="u-js-hide"><a href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#Aff1">1</a></sup>,</li> <li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#auth-William_W_-Hauswirth-Aff2" data-author-popup="auth-William_W_-Hauswirth-Aff2" data-author-search="Hauswirth, William W.">William W. Hauswirth</a><sup class="u-js-hide"><a href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#Aff2">2</a></sup>,</li> <li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#auth-Qiuhong-Li-Aff2" data-author-popup="auth-Qiuhong-Li-Aff2" data-author-search="Li, Qiuhong">Qiuhong Li</a><sup class="u-js-hide"><a href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#Aff2">2</a></sup>,</li> <li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#auth-Thomas_B_-Connor-Aff3" data-author-popup="auth-Thomas_B_-Connor-Aff3" data-author-search="Connor, Thomas B.">Thomas B. Connor</a><sup class="u-js-hide"><a href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#Aff3">3</a></sup>,</li> <li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#auth-James_A_-Kuchenbecker-Aff1" data-author-popup="auth-James_A_-Kuchenbecker-Aff1" data-author-search="Kuchenbecker, James A.">James A. Kuchenbecker</a><sup class="u-js-hide"><a href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#Aff1">1</a></sup>,</li> <li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#auth-Matthew_C_-Mauck-Aff3" data-author-popup="auth-Matthew_C_-Mauck-Aff3" data-author-search="Mauck, Matthew C.">Matthew C. Mauck</a><sup class="u-js-hide"><a href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#Aff3">3</a></sup>,</li> <li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#auth-Jay-Neitz-Aff1" data-author-popup="auth-Jay-Neitz-Aff1" data-author-search="Neitz, Jay" data-corresp-id="c1">Jay Neitz <svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"> <use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium" /> </svg></a><sup class="u-js-hide"><a href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#Aff1">1</a></sup> &amp;</li> <li class="c-article-author-list__show-more" aria-label="Show all 8 authors for this article" title="Show all 8 authors for this article">…</li> <li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#auth-Maureen-Neitz-Aff1" data-author-popup="auth-Maureen-Neitz-Aff1" data-author-search="Neitz, Maureen">Maureen Neitz</a><sup class="u-js-hide"><a href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#Aff1">1</a></sup>&nbsp;</li> </ul><button aria-expanded="false" class="c-article-author-list__button"> <svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"> <use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-down-medium" /> </svg><span>Show authors</span></button> <p class="c-article-info-details" data-container-section="info"><a data-test="journal-link" href="https://www-nature-com.translate.goog/?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB" data-track="click" data-track-action="journal homepage" data-track-category="article body" data-track-label="link"><i data-test="journal-title">Nature</i></a> <b data-test="journal-volume"><span class="u-visually-hidden">volume</span>&nbsp;461</b>,&nbsp;<span class="u-visually-hidden">pages </span>784–787 (<span data-test="article-publication-year">2009</span>)<a href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#citeas" class="c-article-info-details__cite-as u-hide-print" data-track="click" data-track-action="cite this article" data-track-label="link">Cite this article</a></p> <div class="c-article-metrics-bar__wrapper u-clear-both"> <ul class="c-article-metrics-bar u-list-reset"> <li class=" c-article-metrics-bar__item" data-test="access-count"><p class="c-article-metrics-bar__count">12k <span class="c-article-metrics-bar__label">Accesses</span></p></li> <li class="c-article-metrics-bar__item" data-test="citation-count"><p class="c-article-metrics-bar__count">233 <span class="c-article-metrics-bar__label">Citations</span></p></li> <li class="c-article-metrics-bar__item" data-test="altmetric-score"><p class="c-article-metrics-bar__count">153 <span class="c-article-metrics-bar__label">Altmetric</span></p></li> <li class="c-article-metrics-bar__item"><p class="c-article-metrics-bar__details"><a href="https://www-nature-com.translate.goog/articles/nature08401/metrics?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB" data-track="click" data-track-action="view metrics" data-track-label="link" rel="nofollow">Metrics <span class="u-visually-hidden">details</span></a></p></li> </ul> </div> </header> </div> <div class="c-article-body"> <section aria-labelledby="Abs3" data-title="Abstract" lang="en"> <div class="c-article-section" id="Abs3-section"> <h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs3">Abstract</h2> <div class="c-article-section__content" id="Abs3-content"> <p>Red–green colour blindness, which results from the absence of either the long- (L) or the middle- (M) wavelength-sensitive visual photopigments, is the most common single locus genetic disorder. Here we explore the possibility of curing colour blindness using gene therapy in experiments on adult monkeys that had been colour blind since birth. A third type of cone pigment was added to dichromatic retinas, providing the receptoral basis for trichromatic colour vision. This opened a new avenue to explore the requirements for establishing the neural circuits for a new dimension of colour sensation. Classic visual deprivation experiments<sup><a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 1" title="Wiesel, T. N. &amp; Hubel, D. H. Single-cell responses in striate cortex of kittens deprived of vision in one eye. J. Neurophysiol. 26, 1003–1017 (1963)" href="https://www-nature-com.translate.goog/articles/nature08401?_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB#ref-CR1" id="ref-link-section-d45640904e408">1</a></sup> have led to the expectation that neural connections established during development would not appropriately process an input that was not present from birth. Therefore, it was believed that the treatment of congenital vision disorders would be ineffective unless administered to the very young. However, here we show that the addition of a third opsin in adult red–green colour-deficient primates was sufficient to produce trichromatic colour vision behaviour. Thus, trichromacy can arise from a single addition of a third cone class and it does not require an early developmental process. 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'semantic', model: 'specter', policy_id: 'NA', timestamp: 1732754714, embedded_user: 'null' } }); </script> <div> <div id="MagazineFulltextArticleBodySuffix"> <section aria-labelledby="Bib1" data-title="References"> <div class="c-article-section" id="Bib1-section"> <h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Bib1">References</h2> <div class="c-article-section__content" id="Bib1-content"> <div data-container-section="references"> <ol class="c-article-references" data-track-component="outbound reference" data-track-context="references section"> <li class="c-article-references__item js-c-reading-companion-references-item" data-counter="1"><p class="c-article-references__text" id="ref-CR1">Wiesel, T. 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Heeb Foundation, the Posner Foundation, the Macular Vision Research Foundation, the Foundation Fighting Blindness, Hope for Vision, and Research to Prevent Blindness. We would like to thank V. Chiodo, S. Boye, D. Conklyn, P. M. Summerfelt, K. Chmielewski and K. L. Gunther for technical assistance. J.N. is the Bishop Professor in Ophthalmology, M.N. is the Ray Hill Professor in Ophthalmology, and W.W.H. is Rybaczki-Bullard Professor of Ophthalmology.</p> <p><b>Author Contributions</b> Experiments and data analysis were performed by K.M., T.B.C., J.A.K., M.C.M., J.N. and M.N. Cone-specific expression of the gene therapy vector was developed and validated by Q.L., and W.W.H. constructed the vector and packaged it into adeno-associated virus and provided dosage guidance. All authors contributed to data interpretation. The manuscript was written by K.M., J.N. and M.N. and incorporates comments by all others.</p> </div> </div> </section> <section aria-labelledby="author-information" data-title="Author information"> <div class="c-article-section" id="author-information-section"> <h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="author-information">Author information</h2> <div class="c-article-section__content" id="author-information-content"> <h3 class="c-article__sub-heading" id="affiliations">Authors and Affiliations</h3> <ol class="c-article-author-affiliation__list"> <li id="Aff1"><p class="c-article-author-affiliation__address">Department of Ophthalmology, Box 356485, University of Washington, 1959 North East Pacific Street, Seattle, Washington 98195, USA,</p><p class="c-article-author-affiliation__authors-list">Katherine Mancuso,&nbsp;James A. Kuchenbecker,&nbsp;Jay Neitz&nbsp;&amp;&nbsp;Maureen Neitz</p></li> <li id="Aff2"><p class="c-article-author-affiliation__address">Department of Ophthalmology and Powell Gene Therapy Center, University of Florida, 1600 South West Archer Road, Gainesville, Florida 32610, USA,</p><p class="c-article-author-affiliation__authors-list">William W. Hauswirth&nbsp;&amp;&nbsp;Qiuhong Li</p></li> <li id="Aff3"><p class="c-article-author-affiliation__address">Department of Ophthalmology, Medical College of Wisconsin, 925 North 87th Street, Milwaukee, Wisconsin 53226, USA,</p><p class="c-article-author-affiliation__authors-list">Thomas B. Connor&nbsp;&amp;&nbsp;Matthew C. Mauck</p></li> </ol> <div class="u-js-hide u-hide-print" data-test="author-info"> <span class="c-article__sub-heading">Authors</span> <ol class="c-article-authors-search u-list-reset"> <li id="auth-Katherine-Mancuso-Aff1"><span class="c-article-authors-search__title u-h3 js-search-name">Katherine Mancuso</span> <div class="c-article-authors-search__list"> <div class="c-article-authors-search__item c-article-authors-search__list-item--left"> <a href="https://www-nature-com.translate.goog/search?author=Katherine+Mancuso&amp;_x_tr_sl=auto&amp;_x_tr_tl=en&amp;_x_tr_hl=en-GB" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a> </div> <div class="c-article-authors-search__item c-article-authors-search__list-item--right"> <p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="https://translate.google.com/website?sl=auto&amp;tl=en&amp;hl=en-GB&amp;u=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd%3Dsearch%26term%3DKatherine%2520Mancuso" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide">&nbsp;</span><a class="c-article-identifiers__item" href="https://translate.google.com/website?sl=auto&amp;tl=en&amp;hl=en-GB&amp;u=http://scholar.google.co.uk/scholar?as_q%3D%26num%3D10%26btnG%3DSearch%2BScholar%26as_epq%3D%26as_oq%3D%26as_eq%3D%26as_occt%3Dany%26as_sauthors%3D%2522Katherine%2520Mancuso%2522%26as_publication%3D%26as_ylo%3D%26as_yhi%3D%26as_allsubj%3Dall%26hl%3Den" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p> </div> </div></li> <li id="auth-William_W_-Hauswirth-Aff2"><span class="c-article-authors-search__title u-h3 js-search-name">William W. 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