Vorinostat: a potent agent to prevent and treat laser-induced corneal haze.

Purpose: This study investigated the efficacy and safety of vorinostat, a deacetylase (HDAC) inhibitor, in the treatment of laser-induced corneal haze following photorefractive keratectomy (PRK) in rabbits in vivo and transforming growth factor beta 1 (TGFβ1) -induced corneal fibrosis in vitro.

Methods: Corneal haze in rabbits was produced with -9.00 diopters (D) PRK.

Targeted decorin gene therapy delivered with adeno-associated virus effectively retards corneal neovascularization in vivo.

Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno-associated virus serotype 5 (AAV5) impedes corneal neovascularization (CNV) in vivo without significant side effects. An established rabbit CNV model was used.

Gene therapy in the cornea: 2005--present.

Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of access and relative immune-privilege.

Significant inhibition of corneal scarring in vivo with tissue-selective, targeted AAV5 decorin gene therapy.

Purpose: This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the stroma with adeno-associated virus serotype 5 (AAV5) inhibits corneal fibrosis in vivo without significant side effects.

Methods: An in vivo rabbit model of corneal fibrosis was used. Targeted decorin gene therapy was delivered to the rabbit cornea by a single topical application of AAV5 (100 μL; 6.

Efficacious and safe tissue-selective controlled gene therapy approaches for the cornea.

Untargeted and uncontrolled gene delivery is a major cause of gene therapy failure. This study aimed to define efficient and safe tissue-selective targeted gene therapy approaches for delivering genes into keratocytes of the cornea in vivo using a normal or diseased rabbit model. New Zealand White rabbits, adeno-associated virus serotype 5 (AAV5), and a minimally invasive hair-dryer based vector-delivery technique were used.

Polyethylenimine-conjugated gold nanoparticles: Gene transfer potential and low toxicity in the cornea.

Unlabelled: This study examined the gene transfer efficiency and toxicity of 2-kDa polyethylenimine conjugated to gold nanoparticles (PEI2-GNPs) in the human cornea in vitro and rabbit cornea in vivo. PEI2-GNPs with nitrogen-to-phosphorus ratios of up to 180 exhibited significant transgene delivery in the human cornea without altering the viability or phenotype of these cells. Similarly, PEI2-GNPs applied to corneal tissues collected after 12 hours, 72 hours, or 7 days exhibited appreciable gold uptake throughout the rabbit stroma with gradual clearance of GNPs over time.

AAV serotype influences gene transfer in corneal stroma in vivo.

This study evaluated the cellular tropism and relative transduction efficiency of three AAV serotypes, AAV6, AAV8 and AAV9, for corneal gene delivery using mouse cornea in vivo and donor human cornea ex vivo. The AAV6, AAV8 and AAV9 serotypes having AAV2 plasmid encoding for alkaline phosphatase (AP) gene were generated by transfecting HEK 293 cell line with pHelper, pARAP4 and pRep/Cap plasmids. Viral vectors (10(9) vg/microl) were topically applied onto mouse cornea in vivo and human cornea ex vivo after removing the epithelium.