Gene therapy for diseases of the cornea – a review

Abstract

The cornea is particularly suited to gene therapy. The cornea is readily accessible, normally transparent, and is somewhat sequestrated from the general circulation and the systemic immune system. The principle of genetic therapy for the cornea is to use an appropriate vector system to transfer a gene to the cornea itself, or to the ocular environs, or systemically, so that a transgenic protein will be expressed that will modulate congenital or acquired disease. The protein may be structural such as a collagen, or functionally active such as an enzyme, cytokine or growth factor that may modulate a pathological process. Alternatively, gene expression may be silenced by the use of modalities such as antisense oligonucleotides. Interestingly, despite a very considerable amount of work in animal models, clinical translation directed to gene therapy of the human cornea has been minimal. This is in contrast to gene therapy for monogenic inherited diseases of the retina, where promising early results of clinical trials for Leber's congenital amaurosis have already been published and a number of other trials are ongoing.

Vaginal gene therapy

“…These vectors provide high and stable expression, and are able to transfect dividing cells, non-dividing cells and primary cells [48]. Moreover, serious adverse events have not been reported with lentiviral vectors in clinical trials [49]. A lentivirus-based system carrying shRNA have been recently studied as an anti-HIV vaccine [50].…”

Nanomedicine and its role in Ophthalmology

“…Gene therapy can also be used for prevention of cornea rejection, cornea neovascularization and herpetic stromal keratitis. 55 Nanoparticle-based gene therapy is effective for continuous delivery of therapeutic genes and better efficacy because of improved cellular uptake, endosomal escape and transport up to the nucleus. 44 …”

Corneal Gene Therapy in Veterinary Medicine: A Review

“…While MPS is relatively rare in veterinary medicine, the use of dogs in research is not uncommon because they serve as a large animal model for human disease. Corneal pathology typically involves opacification of the cornea due to lysosomal storage in keratocytes [38]. Intravenous gene therapy in neonatal MPS dogs using a retroviral vector has been shown to prevent GAG accrual and resultant corneal clouding.…”

“…The unique setting afforded by having an established tissue bank for corneal transplants is ideal for gene therapy, as donor cornea can easily be manipulated, ex vivo, prior to transplantation. Several gene therapy methods have been examined in an effort to improve graft survival by the delivery of therapeutic genes that modulate cellular apoptosis, angiogenesis, and wound healing [38]. One study investigated the delivery of an intracellular enzyme, indoleamine 2,3-dioxygenase (IDO), using a lentivirus vector in murine corneal endothelium [39].…”