Age-related macular degeneration: how could gene and cell therapy help?

‘Dry’ AMD is more common, accounting for about 85-90% of AMD cases. It involves the gradual loss of cells in the macula, resulting in a slow decline in vision. Small yellowish deposits of proteins and lipids, called drusen accumulate in the macula. These drusen can interfere with the normal function of retinal cells. In advanced stages of ‘dry’ AMD (also known as geographic atrophy), the retinal cells have died. This leads to significant central vision impairment.

‘Wet’ AMD, although less common, is typically more severe.  It involves the growth of abnormal blood vessels beneath the macula, in a tissue called the choroid. This process is called choroidal neovascularisation. These new blood vessels can leak fluid and thus cause rapid vision loss. This type of AMD often manifests as sudden and noticeable changes in the central vision. These changes can include the appearance of dark spots or distorted and wavy lines. Importantly, ‘dry’ AMD can sometimes develop into ‘wet’ AMD upon the presence of these abnormal blood vessels.

Scientists are investigating whether AMD can be treated using gene transfer methods. Theoretically, a successful gene therapy would be a one-off treatment. This would reduce patients’ treatment burder of receiving repeated injections. For example, viral vectors containing genes for VEGF could be injected into the eye. These modified cells would then express the ‘'healthy’' version of this growth factor, [preventing/reducing] choroid neovascularisation.

In order to overcome the burden of repeated injections into the eye with pharmacologic treatments for either wet or dry AMD ,researchers are exploring the possibility of using gene transfer methods. For example, incorporating genes for VEGF or the complement system into virus vectors that are in turn injected into the eye could, in theory, minimise treatment to just one injection. This is because once injected, these virus vectors may use the retinal cells’ own machinery for continuous production of the drug within the eye.

One hallmark of AMD is the disruption and loss of a specific cell layer called the retinal pigment epithelium. This cell layer is important for maintaining a health retina. When this layer does not work correctly, the light-sensing photoreceptors of the eye stop functioning correctly, resulting in significant vision loss.

Stem cells hold promise for treating or slowing down the progression of this process by replacing the damaged retinal cells or by providing protective factors. In the past two decades, extensive work has been put into developing techniques to generate specialised retinal cells, with the goal of transplanting them into the macula to restore lost vision.