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<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
</div>
<div class="action-panel-control-wrap">
<label for="email-from" class="action-panel-label">
From:
</label>
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" 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="4hG1boSV4BExn3FbWJwnLyxxZ0hB7OxDl4q6OelhEcr1huL1z29pfG3bx4ZN0p5X">
<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="4hG1boSV4BExn3FbWJwnLyxxZ0hB7OxDl4q6OelhEcr1huL1z29pfG3bx4ZN0p5X">
<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="4hG1boSV4BExn3FbWJwnLyxxZ0hB7OxDl4q6OelhEcr1huL1z29pfG3bx4ZN0p5X">
<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="4hG1boSV4BExn3FbWJwnLyxxZ0hB7OxDl4q6OelhEcr1huL1z29pfG3bx4ZN0p5X">
<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="4hG1boSV4BExn3FbWJwnLyxxZ0hB7OxDl4q6OelhEcr1huL1z29pfG3bx4ZN0p5X">
<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="21989719">
<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://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.10-5955"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=7898&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=21989719&amp;db=pubmed&amp;nlmid=7703701"
title="See full text options at Silverchair Information Systems"
data-ga-category="full_text"
data-ga-action="Silverchair Information Systems"
data-ga-label="21989719"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--iovs.arvojournals.org-images-IOVS_fulltext.png" alt="Silverchair Information Systems full text link"><span class="text">
Silverchair Information Systems
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/21989719/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=21989719&amp;db=pubmed&amp;nlmid=7703701"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="21989719"
><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="/21989719/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/21989719/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="21989719" 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%2F21989719%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="4hG1boSV4BExn3FbWJwnLyxxZ0hB7OxDl4q6OelhEcr1huL1z29pfG3bx4ZN0p5X"><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
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ADAMTSL4, a secreted glycoprotein widely distributed in the eye, binds fibrillin-1 microfibrils and accelerates microfibril biogenesis
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<h2 class="title">
Abstract
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id="eng-abstract">
<p>
<strong class="sub-title">
Purpose:
</strong>
ADAMTSL4 mutations cause autosomal recessive isolated ectopia lentis (IEL) and ectopia lentis et pupillae. Dominant FBN1 mutations cause IEL or syndromic ectopia lentis (Marfan syndrome and Weill-Marchesani syndrome). The authors sought to characterize recombinant ADAMTSL4 and the ocular distribution of ADAMTSL4 and to investigate whether ADAMTSL4 influences the biogenesis of fibrillin-1 microfibrils, which compose the zonule.
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Methods:
</strong>
ADAMTSL4 was expressed by the transfection of HEK293F cells. Protein extracts and paraffin sections from human eyes were analyzed by Western blot analysis and by immunoperoxidase staining, respectively. Immunofluorescence was used to evaluate fibrillin-1 deposition in the ECM of fetal bovine nuchal ligament cells after culture in ADAMTSL4-conditioned medium or control medium. Confocal microscopy was performed to investigate ADAMTSL4 and fibrillin-1 colocalization in these cultures.
</p>
<p>
<strong class="sub-title">
Results:
</strong>
Western blot analysis identified ADAMTSL4 as a glycoprotein in HEK293F cells and as a major band of 150 kDa in ocular tissues including ciliary body, sclera, cornea, and retina. Immunoperoxidase staining showed a broad ocular distribution of ADAMTSL4, associated with both cells and fibrillar ECM. When cultured in ADAMTSL4-containing medium, fetal bovine nuchal ligament cells showed accelerated fibrillin-1 deposition in ECM. ADAMTSL4 colocalized with fibrillin-1 microfibrils in the ECM of these cells.
</p>
<p>
<strong class="sub-title">
Conclusions:
</strong>
ADAMTSL4 is a secreted glycoprotein that is widely distributed in the human eye. Enhanced fibrillin-1 deposition in the presence of ADAMTSL4 and colocalization of ADAMTSL4 with fibrillin-1 in the ECM of cultured fibroblasts suggest a potential role for ADAMTSL4 in the formation or maintenance of the zonule.
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data-pmc-id="PMC3292378"
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<strong class="figure-label">
<p> Figure 1. </p>
</strong>
<div class="figure-caption-contents"><p> Western blot of recombinant ADAMTSL4.… </p></div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 1. </p>
</strong>
<div class="figure-caption-contents"><p> Western blot of recombinant ADAMTSL4. ( <b> A </b> ) Analysis of medium from HEK293F… </p></div>
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<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 1.
</strong>
<div class="figure-caption-contents">Western blot of recombinant ADAMTSL4. (<b>A</b>) Analysis of medium from HEK293F cells stably transfected with ADAMTSL4 or empty vector shows detectable ADAMTSL4 protein only in ADAMTSL4-transfected cells. <i>Solid arrow</i>: major 140- to 150-kDa species; <i>asterisks</i>: presumed proteolytic fragments. The identities of the 250-kDa species marked by the <i>arrowhead</i> and the species indicated by the <i>broken arrow</i> are unknown, although these species are also attenuated by preblocking the antibody with immunogen peptides (Supplementary Fig. S1A, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.iovs.org/lookup/suppl/doi:10.1167/iovs.10-5955/-/DCSupplemental">http://www.iovs.org/lookup/suppl/doi:10.1167/iovs.10-5955/-/DCSupplemental</ext-link>). (<b>B</b>) Enzymatic deglycosylation of ADAMTSL4 in conditioned medium of stably transfected HEK293F cells was performed using peptide <i>N</i>-glycosidase F. Increased electrophoretic mobility of anti-ADAMTSL4 reactive species is seen in the presence of peptide <i>N</i>-glycosidase F (+) compared with the untreated control (). (<b>C</b>) Enzymatic deglycosylation of ADAMTSL4 in conditioned medium of stably transfected HEK293F cells was performed using <i>O</i>-glycosidase (+). Increased electrophoretic mobility of anti-ADAMTSL4 reactive species is seen after <i>O</i>-glycosidase treatment.</div>
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itemprop="contentUrl"
aria-describedby="figure-caption-1"
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data-image-width="480"
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data-pmc-id="PMC3292378"
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id="article-image-1"
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alt="Figure 2." />
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<strong class="figure-label">
<p> Figure 2. </p>
</strong>
<div class="figure-caption-contents"><p> Immunolocalization of ADAMTSL4 in transiently… </p></div>
</div>
</div>
<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> Immunolocalization of ADAMTSL4 in transiently transfected COS-1 cells. Punctate distribution in ( <b> A… </b> </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">Immunolocalization of ADAMTSL4 in transiently transfected COS-1 cells. Punctate distribution in (<b>A</b>) ECM of nonpermeabilized cells and (<b>B</b>) cytoplasmic staining in permeabilized cells. (<b>A</b>) The plane of focus in (<b>A</b>) is the substratum underneath the imaged cells. The center row demonstrates staining in the subcellular ECM “footprint” left behind by a detached cell; hence, no DAPI stained nuclei are seen here. As a positive control for the staining procedure, and as a representative member of the ADAMTSL family, a punctate staining pattern in ECM was seen in myc-His<sub>6</sub>tagged ADAMTSL1-transfected cells immunostained with anti-myc (<b>C</b>, <i>left</i>). Absence of staining in cells where the primary antibody was omitted (<b>C</b>, <i>right</i>). Scale bars, 50 μm.</div>
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data-image-alt="Figure 3."
data-pmc-id="PMC3292378"
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<img class="figure-thumb" itemprop="thumbnail"
id="article-image-2"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f60/3292378/68e0f09f7062/z7g9991121640003.gif"
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<strong class="figure-label">
<p> Figure 3. </p>
</strong>
<div class="figure-caption-contents"><p> Western blot analysis of various… </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> Western blot analysis of various components dissected from a normal human eye. The… </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">Western blot analysis of various components dissected from a normal human eye. The source for each sample is indicated above the corresponding lanes. The molecular weight markers (in kDa) are shown at the left of each panel. cb, ciliary body; rs, retinal tissue.</div>
</figcaption>
</figure>
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data-image-width="480"
data-image-height="652"
data-image-alt="Figure 4."
data-pmc-id="PMC3292378"
data-figure-id="F4">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-3"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f60/3292378/8fdaccc45f86/z7g9991121640004.gif"
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<strong class="figure-label">
<p> Figure 4. </p>
</strong>
<div class="figure-caption-contents"><p> Localization of ADAMTSL4 in the… </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> Localization of ADAMTSL4 in the anterior segment of a normal human eye. ADAMTSL4… </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">Localization of ADAMTSL4 in the anterior segment of a normal human eye. ADAMTSL4 signal is <i>brown</i>, and the section is counterstained with hematoxylin (<i>blue</i>). (<b>A</b>), (<b>B</b>), (<b>D</b>) and (<b>F</b>) are negative control images corresponding to (<b>A</b>), (<b>B</b>), (<b>D</b>) and (<b>E</b>) were obtained from sections in which the primary antibody was omitted. (<b>A</b>) Cornea. Epithelium (E) and endothelium (En) are indicated. (<b>B</b>) Iris stroma. Signal is primarily seen in fibrillar ECM. (<b>C</b>) Trabecular meshwork (TM). <i>Asterisk</i>: canal of Schlemm. Co, cornea; I, iris. (<b>D</b>) Ciliary body. The unpigmented epithelium is indicated by an <i>arrow</i>. Note that the antibody signal is primarily within the ECM of the ciliary body (see control <b>D</b> and Supplementary Fig. S1B, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.iovs.org/lookup/suppl/doi:10.1167/iovs.10-5955/-/DCSupplemental">http://www.iovs.org/lookup/suppl/doi:10.1167/iovs.10-5955/-/DCSupplemental</ext-link>). (<b>E</b>) Lens shows immunostaining in the lens cortex in the equatorial region. LE, lens epithelium. Scale bars, 50 μm.</div>
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itemprop="contentUrl"
aria-describedby="figure-caption-4"
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data-image-alt="Figure 5."
data-pmc-id="PMC3292378"
data-figure-id="F5">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-4"
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<strong class="figure-label">
<p> Figure 5. </p>
</strong>
<div class="figure-caption-contents"><p> Localization of ADAMTSL4 in the… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 5. </p>
</strong>
<div class="figure-caption-contents"><p> Localization of ADAMTSL4 in the posterior segment of a normal human eye. ADAMTSL4… </p></div>
</div>
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 5.
</strong>
<div class="figure-caption-contents">Localization of ADAMTSL4 in the posterior segment of a normal human eye. ADAMTSL4 signal is <i>brown</i>, and the sections are counterstained with hematoxylin (<i>blue</i>). (<b>AE</b>) From sections stained without primary antibody as a negative control. (<b>AE</b>) Stained sections. (<b>A</b>) Retina. OFL, optic fiber layer; GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; PRL, photoreceptor layer, RPE, retinal pigment epithelium. (<b>B</b>) Ch, choroid; Sc, sclera. (<b>C</b>) Sclera. (<b>D</b>) Optic nerve. Note ADAMTSL4 staining in ECM of sclera, choroid, and optic nerve. (<b>E</b>) Retinal blood vessel. <i>Arrows</i>: cellular staining in vascular smooth muscle cells. Scale bars, 50 μm.</div>
</figcaption>
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data-image-alt="Figure 6."
data-pmc-id="PMC3292378"
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<strong class="figure-label">
<p> Figure 6. </p>
</strong>
<div class="figure-caption-contents"><p> ADAMTSL4 accelerates fibrillin-1 deposition in… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 6. </p>
</strong>
<div class="figure-caption-contents"><p> ADAMTSL4 accelerates fibrillin-1 deposition in the matrix of cultured fibroblasts. Fetal bovine nuchal… </p></div>
</div>
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 6.
</strong>
<div class="figure-caption-contents">ADAMTSL4 accelerates fibrillin-1 deposition in the matrix of cultured fibroblasts. Fetal bovine nuchal ligament cells (fBNL) cells were cultured to confluence in media that had previously been conditioned by HEK293F cells stably transfected with ADAMTSL4 expression plasmid or empty vector as indicated. After 4 days of culture, cells were fixed and stained for fibrillin-1 (<i>green</i>), and nuclei were stained with DAPI (<i>blue</i>). Three representative fields (20× magnification) from independent experiments are shown for both vector-conditioned and ADAMTSL4-conditioned mediumtreated fBNL cells. Note the enhanced fibrillin-1 fluorescence in cells cultured in the presence of exogenous ADAMTSL4. Scale bars, 50 μm.</div>
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data-pmc-id="PMC3292378"
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<img class="figure-thumb" itemprop="thumbnail"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f60/3292378/6cff76d0fe00/z7g9991121640007.gif"
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<strong class="figure-label">
<p> Figure 7. </p>
</strong>
<div class="figure-caption-contents"><p> ADAMTSL4 colocalizes with fibrillin-1 microfibrils… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 7. </p>
</strong>
<div class="figure-caption-contents"><p> ADAMTSL4 colocalizes with fibrillin-1 microfibrils in ECM of cultured fibroblasts. Combined immunofluorescence for… </p></div>
</div>
<figcaption id="figure-caption-6" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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Figure 7.
</strong>
<div class="figure-caption-contents">ADAMTSL4 colocalizes with fibrillin-1 microfibrils in ECM of cultured fibroblasts. Combined immunofluorescence for ADAMTSL4 (<i>red</i>) and fibrillin-1 (<i>green</i>) was performed after culture of fBNL cells in the presence of ADAMTSL4-conditioned medium or without the addition of conditioned medium. (<b>A</b>) Confocal microscopy. In ADAMTSL4 mediumtreated cells, confocal images show that ADAMTSL4 distribution overlaps with fibrillin-1 (<i>yellow</i>, <i>merged image</i>). (<b>B</b>) Conventional fluorescence microscopy. Cells were incubated with vector-conditioned medium. ADAMTSL4 was also detected in these cultures and colocalized with fibrillin-1 immunostaining (<i>yellow</i>), suggesting the production of ADAMTSL4 by fBNL cells or HEK293F cells. (<b>C</b>) fBNL cultures were grown without the addition of any conditioned medium. Note the presence of ADAMTSL4 on fibrillin-1 microfibrils, indicating the production of ADAMTSL4 by fBNL cells (see Supplementary Fig. S2, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.iovs.org/lookup/suppl/doi:10.1167/iovs.10-5955/-/DCSupplemental">http://www.iovs.org/lookup/suppl/doi:10.1167/iovs.10-5955/-/DCSupplemental</ext-link>). Scale bars, 50 μm.</div>
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Substances
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<div id="related-links" class="related-links">
<h2 class="title">
Related information
</h2>
<ul class="related-links-list"><li><a title="PubMed links associated with Books" href="https://www.ncbi.nlm.nih.gov/books?linkname=pubmed_books_refs&amp;from_uid=21989719"
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Cited in Books
</a></li><li><a title="Link to related Genes" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene&amp;from_uid=21989719"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=21989719&ordinalpos=1&linkpos=2">
Gene
</a></li><li><a title="Link to Gene for the GeneRIF subcategory" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene_rif&amp;from_uid=21989719"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=21989719&ordinalpos=1&linkpos=3">
Gene (GeneRIF)
</a></li><li><a title="Related information in MedGen" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen&amp;from_uid=21989719"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=21989719&ordinalpos=1&linkpos=4">
MedGen
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=21989719&ordinalpos=1&linkpos=5">
MedGen (Bookshelf cited)
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=21989719&ordinalpos=1&linkpos=6">
OMIM (cited)
</a></li><li><a title="Published protein sequences" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein&amp;from_uid=21989719"
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=21989719&ordinalpos=1&linkpos=7">
Protein
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=21989719&ordinalpos=1&linkpos=8">
Protein (RefSeq)
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<div id="grants" class="grants">
<h2 class="title">
Grants and funding
</h2>
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