Minimizing side effects of ballistic gene transfer into the murine corneal epithelium

Abstract

Ballistic gene transfer into the corneal epithelium allows high cytokine expression in the cornea without measurable side effects if an apparatus is used that is adapted for this specific purpose.

Influence of ballistic gene transfer on antigen-presenting cells in murine corneas

“…Holland described the kinetic changes affecting inflammatory cells and MHC antigenic markers in rat syngeneic and allogeneic corneal grafts [14]. Previous experiments showed massive macrophage and granulocyte infiltration on the third postoperative day after syngeneic or allogeneic corneal transplantation due to surgical irritation [44]. These recipient APCs infiltrate the graft then migrate to the draining node bearing donor-alloantigen-derived peptides on their MHC molecules.…”

Gene therapy for corneal graft survival

“…Intrastromal injection of naked DNA Epithelium, stromal cells (in vivo) 5 [36] Ultrasound and microbubbles Stromal cells (in vivo) 1 4 [40] Electroporation Stromal cells (in vivo) 1 0 [37,38,41] Gene gun Epithelium (in vivo) 5 [42][43][44][45][46][47] Synthetic peptide (DNA/polylisinemolossin/fusogenic peptide) Endothelium (ex vivo) 7 [48] Dendrimers (polyamidoamine) Endothelium (ex vivo) 5-10 [49] Liposomes Epithelium, keratocytes and endothelium 7 [50][51][52][53] Antibody-targeted liposomes (transferrin and E-selectin) Endothelium (ex vivo) 10-15 [39,54] Dehydrated plasmids (p-bFGF-polyethylenimine)…”

Synthetic nanocarriers for the delivery of polynucleotides to the eye

“…While the ocular delivery of polynucleotides has been achieved by physical means, such as electroporation (Blair-Parks et al, 2002;Hao et al, 2009), iontophoresis (Berdugo et al, 2003;Hao et al, 2009), gene gun (Tanelian et al, 1997;Zhang et al, 2002) and sonophoresis (Yamashita et al, 2007), the use of nanocarriers offers specific advantages, such as (i) their nanometric size and components properties may allow their transport in the conjunctival and corneal epithelium (Amrite and Kompella, 2005), (ii) they may provide a sustained delivery of polynucleotides in vivo (Cohen et al, 2000;dos Santos et al, 2006a;Khan et al, 2004) and, (iii) they may target the cornea, the conjunctiva or both (de la Fuente et al, 2008a;de la Fuente et al, 2008b).…”