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<label for="email-from" class="action-panel-label">
From:
</label>
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="pObcRkAc7hGUubOl3RHXeYy0FpgbnYqfGBVhua3yHStooCUbGakZI64EdtYngzYz">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="pObcRkAc7hGUubOl3RHXeYy0FpgbnYqfGBVhua3yHStooCUbGakZI64EdtYngzYz">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="pObcRkAc7hGUubOl3RHXeYy0FpgbnYqfGBVhua3yHStooCUbGakZI64EdtYngzYz">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="pObcRkAc7hGUubOl3RHXeYy0FpgbnYqfGBVhua3yHStooCUbGakZI64EdtYngzYz">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="pObcRkAc7hGUubOl3RHXeYy0FpgbnYqfGBVhua3yHStooCUbGakZI64EdtYngzYz">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="10869443">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://www.pnas.org/doi/10.1073/pnas.150236297?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub 0pubmed"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=4487&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=10869443&amp;db=pubmed&amp;nlmid=7505876"
title="See full text options at Atypon"
data-ga-category="full_text"
data-ga-action="Atypon"
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><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--pnas.org-pb-assets-images-pubmed-pnas-pubmed-fulltext.png" alt="Atypon full text link"><span class="text">
Atypon
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/10869443/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=10869443&amp;db=pubmed&amp;nlmid=7505876"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="10869443"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/10869443/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/10869443/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="10869443" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F10869443%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="pObcRkAc7hGUubOl3RHXeYy0FpgbnYqfGBVhua3yHStooCUbGakZI64EdtYngzYz"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
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<p>
Mutations in the retinal pigment epithelium gene encoding RPE65 are a cause of the incurable early-onset recessive human retinal degenerations known as Leber congenital amaurosis. Rpe65-deficient mice, a model of Leber congenital amaurosis, have no rod photopigment and severely impaired rod physiology. We analyzed retinoid flow in this model and then intervened by using oral 9-cis-retinal, attempting to bypass the biochemical block caused by the genetic abnormality. Within 48 h, there was formation of rod photopigment and dramatic improvement in rod physiology, thus demonstrating that mechanism-based pharmacological intervention has the potential to restore vision in otherwise incurable genetic retinal degenerations.
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<p> Figure 1 </p>
</strong>
<div class="figure-caption-contents"><p> Retinoid and rhodopsin analysis in… </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
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<p> Figure 1 </p>
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<div class="figure-caption-contents"><p> Retinoid and rhodopsin analysis in <i> Rpe65 </i> mice. ( <i> A </i> ) Chromatogram of retinoids… </p></div>
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Figure 1
</strong>
<div class="figure-caption-contents">Retinoid and rhodopsin analysis in <i>Rpe65</i> mice.
(<i>A</i>) Chromatogram of retinoids extracted from eyes of
<i>Rpe65</i>+/+, <i>Rpe65</i>+/, and
<i>Rpe65</i>/ mice. The extraction procedures and
derivatization with hydroxylamine to improve quantitative extraction of
retinaldehydes were described previously (see ref. 13). Peaks are
represented as follows: (1, 2) all-<i>trans</i>-retinyl and
11-<i>cis</i>-retinyl esters (truncated to fit in scale);
(3,3) <i>anti</i>- and <i>syn</i>- of
11-<i>cis</i>-retinal oximes; (4,4) <i>anti</i>- and
<i>syn</i>- of all-<i>trans</i>-retinal oximes; (5)
11-<i>cis</i>-retinol, and (6)
all<i>-trans</i>-retinol. (<i>B</i>) Difference
spectrum of bleached rhodopsin and rhodopsin extracted from eyes of
<i>Rpe65</i>+/ and <i>Rpe65</i>/ mice. The
level of rhodopsin in <i>Rpe65</i>+/ mice is within the
range of rhodopsin found in control <i>Rpe65</i>+/+ mice
(●) and undetectable in
<i>Rpe65</i>/ mice. (<i>C</i>) Aberrant kinetics
of retinoid and rhodopsin recovery in <i>Rpe65</i>+/ mice
after a flash. Photolyzed rhodopsin releases
all-<i>trans</i>-retinal (<i>a</i>), which is reduced
to all-<i>trans</i>-retinol (<i>b</i>), and then
transported to the RPE and esterified to retinyl esters
(<i>c</i>). All-<i>trans</i>-retinol, or its
derivative, is isomerized to 11-<i>cis</i>-retinol
(<i>d</i>), which in turn, is oxidized to
11-<i>cis</i>-retinal (<i>e</i>). The rates of retinoid
formations are compared to the rate obtained for
<i>Rpe65</i>+/+ mice (<img class="formula-image" alt="formula image" src="https://cdn.ncbi.nlm.nih.gov/corehtml/pmc/pmcents/pc-E063.gif"/>).</div>
</figcaption>
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itemprop="contentUrl"
aria-describedby="figure-caption-1"
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data-image-width="410"
data-image-height="679"
data-image-alt="Figure 2"
data-pmc-id="PMC26998"
data-figure-id="F2">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-1"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3b0/26998/4ddc5abf1a2a/pq1502362002.gif"
alt="Figure 2" />
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<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
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<strong class="figure-label">
<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><p> Formation of isorhodopsin and kinetics… </p></div>
</div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><p> Formation of isorhodopsin and kinetics of the retinoid flow in <i> Rpe65 </i> / mice… </p></div>
</div>
<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 2
</strong>
<div class="figure-caption-contents">Formation of isorhodopsin and kinetics of the retinoid flow in
<i>Rpe65</i>/ mice 48 h after
9-<i>cis</i>-retinal gavage. (<i>A</i>) Comparison
spectra of rhodopsin from <i>Rpe65</i>+/+ mice and
isorhodopsin from <i>Rpe65</i>/ mice 48 h after
9-<i>cis</i>-retinal gavage (2.5 mg). Arrows denote differences
in the absorption maximum for rhodopsin and isorhodopsin.
(<i>B</i>) Isorhodopsin formation in
<i>Rpe65</i>/ mice at different time points after 0.5 mg
or 2.5 mg of 9-<i>cis</i>-retinal gavage (<i>n</i>
= 2). (<i>C</i>) Chromatograms illustrate the dark recovery of
retinoids in <i>Rpe65</i>/ mice 48 h after
9-<i>cis</i>-retinal gavage (2.5 mg) after a flash that
bleached ≈45% of isorhodopsin. (<i>C</i>,
<i>Inset</i>) isomeric composition of retinyl esters (8,
9-<i>cis</i>-retinol). (<i>D</i>) Dark recovery of
isorhodopsin in <i>Rpe65</i>/ mice 48 h after
9-<i>cis</i>-retinal gavage after a flash. For comparison, dark
recovery of rhodopsin is shown for <i>Rpe65</i>+/+ (open
hexagons) (7, 7). <i>anti</i>- and <i>syn</i>- of
9-<i>cis</i>-Retinal oximes; all other peaks are as in the Fig.
1 legend.</div>
</figcaption>
</figure>
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itemprop="associatedMedia"
data-slide-index="2"
data-label-slug="figure-3">
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itemprop="contentUrl"
aria-describedby="figure-caption-2"
role="button"
data-image-width="411"
data-image-height="501"
data-image-alt="Figure 3"
data-pmc-id="PMC26998"
data-figure-id="F3">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-2"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3b0/26998/6014a035430e/pq1502362003.gif"
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<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
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<strong class="figure-label">
<p> Figure 3 </p>
</strong>
<div class="figure-caption-contents"><p> Restoration of retinal function in… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 3 </p>
</strong>
<div class="figure-caption-contents"><p> Restoration of retinal function in <i> Rpe65 </i> / mice 48 h after 9- <i> cis… </i> </p></div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 3
</strong>
<div class="figure-caption-contents">Restoration of retinal function in <i>Rpe65</i>/
mice 48 h after 9-<i>cis</i>-retinal gavage.
(<i>A</i> and <i>B</i>) Serial ERG recordings in an
<i>Rpe65</i>/ mouse before and 48 h after
9-<i>cis</i>-retinal gavage compared to a representative
<i>Rpe65</i>+/+ mouse. (<i>A</i>) Dark-adapted ERGs
to increasing intensities of blue light stimuli (shown to the left of
the traces) in an <i>Rpe65</i>/ mouse show an elevated
b-wave threshold compared to <i>Rpe65</i>+/+. The same
stimuli after 9-<i>cis</i>-retinal treatment elicit ERGs at a
lower threshold and with larger amplitude b-waves. (<i>B</i>)
Leading edges (initial 415 ms depending on response) of dark-adapted
ERG photoresponses (symbols) evoked by 3.6 and 2.2 log
scot-cd⋅s⋅m<sup>2</sup> flashes are fit with a model of
phototransduction (smooth lines). The amplitude and sensitivity of the
<i>Rpe65</i>/ mouse photoresponses are reduced. After
9-<i>cis</i>-retinal treatment, photoresponses have larger
amplitude and higher sensitivity. (<i>C</i>) Photoresponses in
three <i>Rpe65</i>+/+ mice are compared to an untreated group
of <i>Rpe65</i>/ mice and a treated group of
<i>Rpe65</i>/ mice. Lines are the model of rod
phototransduction activation fitted to a pair of photoresponses; only
maximal responses are shown for clarity. (<i>D</i>) Maximum
amplitude and sensitivity parameters of dark-adapted photoresponses in
untreated and treated (48 h after 9-<i>cis</i>-retinal gavage)
<i>Rpe65</i>/ mice compared to the results in
<i>Rpe65</i>+/+ mice. Untreated animals have significant
differences (**, <i>P</i> &lt; 0.05) in both
parameters when compared to <i>Rpe65</i>+/+ or treated
<i>Rpe65</i>/ mice. Error bars represent 1 SEM and are
smaller than symbols for some data.</div>
</figcaption>
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data-slide-index="3"
data-label-slug="figure-4">
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itemprop="contentUrl"
aria-describedby="figure-caption-3"
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data-image-width="407"
data-image-height="534"
data-image-alt="Figure 4"
data-pmc-id="PMC26998"
data-figure-id="F4">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-3"
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alt="Figure 4" />
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<strong class="figure-label">
<p> Figure 4 </p>
</strong>
<div class="figure-caption-contents"><p> Human phenotype of putative null… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 4 </p>
</strong>
<div class="figure-caption-contents"><p> Human phenotype of putative null mutation in <i> RPE65 </i> . ( <i> A </i> ) Kinetic… </p></div>
</div>
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 4
</strong>
<div class="figure-caption-contents">Human phenotype of putative null mutation in <i>RPE65</i>.
(<i>A</i>) Kinetic visual fields with a V-4e test target in the
homozygote (black line) compared to normal (gray region); concentric
circles are at 10<sup>o</sup> intervals and meridians are at
15<sup>o</sup>. (<i>B</i>) White stimulus thresholds of the
homozygote (●) shows &gt;6 log units of elevation
under dark-adapted (DA) and &gt;2 log units of elevation under
light-adapted (2.7 log troland) conditions. Normal thresholds (gray
symbols) on increasing background intensities (▿) and during the cone
plateau following a full bleach (▵) are fit with empirical
models of background adaptation (gray lines) to define the rod- and
cone-mediated limbs. The normal cone adaptation model was shifted by
3.8 log units to the right and up to fit the patient data (solid line).
(<i>C</i>) Cone flicker ERGs in homozygote are reduced
≈100-fold in amplitude and abnormally delayed in timing (arrows).
Vertical gray lines mark stimulus times. A 29-Hz sinusoid was fitted to
the homozygote data (dashed lines) to estimate amplitude and timing of
the small signal. (<i>D</i>) Vertical OCT cross-sectional
retinal images through the fovea (9<sup>o</sup> inferior to
6<sup>o</sup> superior retina) show central retinal structure is
generally intact in the homozygote (compared to a heterozygous sibling)
except for thinning of the outer retina-choroid complex, the
red/white band toward bottom of panel. Optical reflectivity of
retinal tissue is shown on a logarithmic pseudocolor scale: red and
white are high reflectivity and blue and black are low reflectivity.
Vitreous is toward the top and sclera is toward the bottom.</div>
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