title: Gene therapy for ocular diseases meditated by ultrasound and microbubbles (Review).
abstract: The eye is an ideal target organ for gene therapy as it is easily accessible and immune‑privileged. With the increasing insight into the underlying molecular mechanisms of ocular diseases, gene therapy has been proposed as an effective approach. Successful gene therapy depends on efficient gene transfer to targeted cells to prove stable and prolonged gene expression with minimal toxicity. At present, the main hindrance regarding the clinical application of gene therapy is not the lack of an ideal gene, but rather the lack of a safe and efficient method to selectively deliver genes to target cells and tissues. Ultrasound‑targeted microbubble destruction (UTMD), with the advantages of high safety, repetitive applicability and tissue targeting, has become a potential strategy for gene‑ and drug delivery. When gene‑loaded microbubbles are injected, UTMD is able to enhance the transport of the gene to the targeted cells. High‑amplitude oscillations of microbubbles act as cavitation nuclei which can effectively focus ultrasound energy, produce oscillations and disruptions that increase the permeability of the cell membrane and create transient pores in the cell membrane. Thereby, the efficiency of gene therapy can be significantly improved. The UTMD‑mediated gene delivery system has been widely used in pre‑clinical studies to enhance gene expression in a site‑specific manner in a variety of organs. With reasonable application, the effects of sonoporation can be spatially and temporally controlled to improve localized tissue deposition of gene complexes for ocular gene therapy applications. In addition, appropriately powered, focused ultrasound combined with microbubbles can induce a reversible disruption of the blood‑retinal barrier with no significant side effects. The present review discusses the current status of gene therapy of ocular diseases as well as studies on gene therapy of ocular diseases meditated by UTMD.
authors.affiliation: Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Wan
authors.affiliation: Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D005128:Eye Diseases / Q000235:genetics / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D045423:Microbubbles; D014465:Ultrasonics / Q000379:methods*