Effective mobilisation of bone marrow-derived cells through proteolytic activity: A new treatment strategy for age-related macular degeneration

Abstract

Selective targeting of bone marrow-derived cells (BMCs) has been heralded as a promising avenue for age-related macular degeneration (AMD) therapeutics. Many researchers have demonstrated that the function of circulating BMCs is related to disease severity in patients with AMD. Transplanted BMCs are able to transdifferentiate into retina-specific cells to replace those lost due to damage or degeneration in the pathologic process of experimental models of AMD, which may provide beneficial effects in patients with AMD. However, a major barrier to transferring the use of BMCs into clinical practice is the limited quantity of BMCs in the peripheral circulation. Technology has not yet reached a stage where ex vivo-expanded BMCs can be routinely used for cell therapy. A feasible strategy to circumvent this issue of BMC scarcity is to increase the mobilisation of autologous BMCs from the patient’s bone marrow into the blood circulation. Extensive studies have demonstrated that the SDF-1/CXCR4 axis is a key regulator for BMC mobilisation. Moreover, abrogation of the SDF-1/CXCR4 axis by proteolytic modification can efficiently increase BMC mobilisation. We speculate that BMC mobilisation by proteolytic enzymes may supply a sufficient amount of autologous cells to repair and regenerate injured and degenerated the retinal pigment epithelium (RPE), photoreceptors, or other retina-specific cells, which could prevent AMD progression. If the BMC mobilisation strategy is used to treat AMD, it may overcome the existing problems of transferring BMC-based therapy into the clinic and become a particularly feasible therapeutic approach for AMD.