"Regeneration medicine applications on age-related macular degeneration"

Abstract

Despite recent advances in diagnosis and treatment, age-related macular degeneration (AMD) remains the commonest cause of blindness in the developed world. Anti-VEGF agents are the mainstay of treatment of the neovascular form of the disease but they cannot reverse visual loss and they have a short time of action, so repeated injections are needed.

There has been a significant research interest in the use of cell replacement therapies in AMD in order to reverse loss of vision. The outer retina is ideal for applying cellular therapies since it is surgically accessible, easily observable and has a relatively simple architecture. A broad range of cells have been tested but predominantly pluripotent stem cells have been used. These have been differentiated into retinal pigment epithelium (RPE) cells and transplanted as cell suspensions or cell sheets under the retina. The first clinical trials of RPE cell replacement have demonstrated the safety of the method and hinted on possible efficacy. Further research is needed in order to tackle issues such as immune rejection and ensure long-term graft survival and maximal efficacy.

Gene therapy could also provide therapeutic options for patients with AMD. Gene transfer via viral vectors may enable the potential for continuous production of antiangiogenetic proteins thus avoiding the need for repeated anti-VEGF injections. Gene silencing with RNA interference has been tested in various clinical trials and could act synergistically with current anti-VEGF treatments. Even though the use of gene editing tools such as CRISPR-Cas is currently limited to preclinical studies, it has been shown to be effective in treating neovascularization in animal models.

GORGOLI Konstantina