Abstract
The cornea is a transparent, avascular tissue that acts as the major refractive surface of the eye. Corneal transparency, assured by the inner stroma, is vital for this role. Disruption in stromal transparency can occur in some inherited or acquired diseases. As a consequence, light entering the eye is blocked or distorted, leading to decreased visual acuity. Possible treatment for restoring transparency could be via viral-based gene therapy. The stroma is particularly amenable to this strategy due to its immunoprivileged nature and low turnover rate. We assayed the potential of AAV vectors to transduce keratocytes following intra-stromal injection in vivo in the mouse cornea and ex vivo in human explants. In murine and human corneas, we transduced the entire stroma using a single injection, preferentially targeted keratocytes and achieved long-term gene transfer (up to 17 months in vivo in mice). Of the serotypes tested, AAV2/8 was the most promising for gene transfer in both mouse and man. Furthermore, transgene expression could be transiently increased following aggression to the cornea.
Highlights
The cornea is the transparent, avascular tissue at the front of the eye that covers the iris
One-week post-administration, enhanced green fluorescent protein (EGFP) fluorescence was detected in the eyes injected with AAV2/1 (Fig. 1a,b) and AAV2/8 (Fig. 1m,n), and epifluorescence continued to increase over one month (Figs. 1c,d and 1o,p, respectively)
The EGFP signal was stronger with the AAV2/8 vector
Summary
The cornea is the transparent, avascular tissue at the front of the eye that covers the iris. As well as acting as a protective barrier to physical and pathogenic injury, the cornea is the major refractive surface of the eye [1]. It is primarily composed of three zones: an external stratified epithelium, a thick collagenous stroma, and a cuboidal monolayer of epithelial-like cells called endothelium. The endothelium is a non-regenerative monolayer of cells, which forms a leaky barrier regulating the hydration of the cornea. In the centre of the cornea is the stroma, which is primarily composed of an extracellular matrix and makes up 90% of the corneal thickness. The predominant residing stromal cell type is the keratocyte, a type of specialised fibroblast, which plays a role in general repair and maintenance [2]
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