Molecular Engineering and its Application in Ophthalmology

Abstract

Gene therapy is the insertion, alteration or removal of genes within an individual's cells and biological tissues to treat disease. The most common form of genetic engineering involves the insertion of a functional gene at an unspecified location in the host genome. This is accomplished by isolating and copying the gene of interest, generating a construct containing all the genetic elements for correct expression, and then inserting this construct into a random location in the host organism. The eye has a number of advantages as a target organ for gene delivery. It is easily accessible; tissue can be examined in vivo by ophthalmoscope; blood retinal and blood aqueous barriers concentrate vectors in the target area and reduce the spread outside the eye. The eye can be used in testing gene delivery to different tissues e.g. endothelium (cornea), epithelium (cornea, ciliary body and iris), muscle (ciliary body), neurons (retina) or even the brain whose neurons are more difficult targets than those in the neuroretina. The methods used to introduce recombinant DNA into cells can be divided into two broad categories; viral vectors and non-viral vectors. 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.