{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:08:17Z","timestamp":1791198497770,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2010,11,23]],"date-time":"2010-11-23T00:00:00Z","timestamp":1290470400000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>We have developed a nonviral gene therapy method based on the electrotransfer of plasmid in the ciliary muscle. These easily accessible smooth muscle cells could be turned into a biofactory for any therapeutic proteins to be secreted in a sustained manner in the ocular media.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Electrical conditions, design of electrodes, plasmid formulation, method and number of injections were optimized <jats:italic>in vivo<\/jats:italic> in the rat by localizing \u03b2\u2010galactosidase expression and quantifying reporter (luciferase) and therapeutic (anti\u2010tumor necrosis factor) proteins secretion in the ocular media. Anatomical measurements were performed via human magnetic resonance imaging to design a human eye\u2010sized prototype that was tested in the rabbit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the rat, transscleral injection of 30 \u00b5g of plasmid diluted in half saline (77 m<jats:sc>M<\/jats:sc> NaCl) followed by application of eight square\u2010wave electrical pulses (15 V, 10 ms, 5.3 Hz) using two platinum\/iridium electrodes, an internal wire and an external sheet, delivered plasmid efficiently to the ciliary muscle fibers. Gene transfer resulted in a long\u2010lasting (at least 5 months) and plasmid dose\u2010\/injection number\u2010 dependent secretion of different molecular weight proteins mainly in the vitreous, without any systemic exposure. Because ciliary muscle anatomical measurements remained constant among ages in adult humans, an integrated device comprising needle\u2010electrodes was designed and manufactured. Its usefulness was validated in the rabbit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Plasmid electrotransfer to the ciliary muscle with a suitable medical device represents a promising local and sustained protein delivery system for treating posterior segment diseases, avoiding repeated intraocular injections. Copyright \u00a9 2010 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.1517","type":"journal-article","created":{"date-parts":[[2010,11,24]],"date-time":"2010-11-24T10:26:34Z","timestamp":1290594394000},"page":"904-919","source":"Crossref","is-referenced-by-count":22,"title":["The ciliary smooth muscle electrotransfer: basic principles and potential for sustained intraocular production of therapeutic 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