Table IV. Ocular Gene Delivery Targeting Growth Factors.
| Type | Mechanism of action | Effect/treatment | Ref |
|---|---|---|---|
| AS-ODN | Targets stop codon of 5′ untranslated region of the mRNA | Decreases protein expression to treat retinal neovascularization | (234) |
| Phosphorothioate AS-ODN | Decreases VEGF levels by 65% | Tested in vitro (hypoxic condition) and iv vivo (inhibit CNV) in a rat models | (235) |
| AS-ODN | inhibits raf kinases | decreases RPE cell proliferation | (236) |
| Modified pegaptanib Sodium | Better pharmacokinetic parameters and less degradation by exonucleases | Shows extremely higher affinity towards to VEGF165 | (237) |
| siRNA | Down regulation of VEGF | Tested in vivo (subretinal administration in mice) | (238) |
| siRNA | Inhibits the expression of VEGF | Tested in vitro (ARPE-19 cells) and in vivo on (corneal angiogenesis) | (239) |
| AS-ODN | Decreases the conjunctival scarring | Useful in glaucoma filtration surgery | (240) |
| Anti-TGFβ32 aptamer (ARC81) | Inhibits fibroblast migration and decreases matrix deposition | Tested in vitro (mink lung epithelial cell proliferation) and in vivo (inhibits endogenously derived TGFβ2 in rabbit ocular fluid matrix) | (241) |
| Phosphorothioate AS-ODN | Inhibits bFGF-induced angiogenesis | Studied to treat rabbit corneal neovascularization | (242) |
| Phosphorothioate AS-ODN | Inhibits fibronectin | Studied to treat diabetic retinopathy in a rat model | (243) |
| AS-ODN | Targets immediate-early (IE) transcriptional unit | Anti-HSV | (244, 245) |
| Modified 12-mer methylphosphonate | Targeted intron/exon junction of the splice acceptor | Greater affinity and selectivity for HSV- 1 | (246) |
| Phosphodiester AS-ODN | Targets translation start site of IE 110 mRNA | Minimizes non specific effects | (247) |
| AS-ODN | Targeting the tumor necrosis factor alpha (TNFα) | Treatment of HSK | (247) |
| AS-ODN (21-mer, ISIS 2922 Vitravene®) | Targeted to coding region of IE 2 | Inhibits CMV | (248) |
| ISIS 13312 (A modified Vitravene®) | Improves the ocular retention of the AS-ODN | With similar bioactivity to Vitravene®, Its half life was in monkey was 2 months greater | (249, 250) |
AS-ODN Anti sense oligonucleotide, HSK herpetic stromal keratitis, HSV herpes simplex virus, CNV choroidal neovascularization, CMV cytomegalovirus