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Plasmid electrotransfer of eye ciliary muscle: principles and therapeutic efficacy using hTNF‐α soluble receptor in uveitis
Author(s) -
Bloquel Carole,
Bejjani Riad Antoine,
Bigey Pascal,
Bedioui Fethi,
Doat Marc,
BenEzra David,
Scherman Daniel,
BeharCohen Francine
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4737fje
Subject(s) - ciliary muscle , ciliary body , gene delivery , transgene , genetic enhancement , uveitis , receptor , inflammation , recombinant dna , secretion , transfection , reporter gene , biology , cilium , pharmacology , microbiology and biotechnology , medicine , immunology , pathology , gene expression , gene , endocrinology , biochemistry , neuroscience , accommodation
Due to its small size and particular isolating barriers, the eye is an ideal target for local therapy. Recombinant protein ocular delivery requires invasive and painful repeated injections. Alternatively, a transfected tissue might be used as a local producer of transgene‐encoded therapeutic protein. We have developed a nondamaging electrically mediated plasmid delivery technique (electrotransfer) targeted to the ciliary muscle, which is used as a reservoir tissue for the long‐lasting expression and secretion of therapeutic proteins. High and long‐lasting reporter gene expression was observed, which was restricted to the ciliary muscle. Chimeric TNF‐α soluble receptor (hTNFR‐Is) electrotransfer led to elevated protein secretion in aqueous humor and to drastic inhibition of clinical and histological inflammation scores in rats with endotoxininduced uveitis. No hTNFR‐Is was detected in the serum, demonstrating the local delivery of proteins using this method. Plasmid electrotransfer to the ciliary muscle, as performed in this study, did not induce any ocular pathology or structural damage. Local and sustained therapeutic protein production through ciliary muscle electrotransfer is a promising alternative to repeated intraocular protein administration for a large number of inflammatory, degenerative, or angiogenic diseases.