Conditioned media from dental pulp stem cells to counteract the age-related macular degeneration

Aims/Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. To date, there are no effective therapies to counteract the AMD towards the most severe stages characterized by a progressive loss of photoreceptors triggered by retinal pigmented epithelium dysfunction. Given their easily source and their high proliferative potential, Dental Pulp Stem Cells (DPSCs) showed promise for regenerative medicine. The main advantage of DPSCs is related to their immunosuppressive and immunoregulatory abilities, including the capability to promote regeneration of damaged tissues. It is well known the therapeutic potential of DPSCs secretome (conditioned media, CM), including trophic factors and cytokines, as a treatment of neurogenerative diseases. We evaluated the capability of DPSCs-CM cultured in hypoxia and normoxic conditions to counteract retinal degeneration in an animal model of AMD.

Methods: DPSCs-CM were intravitreally injected the day before the exposure of albino rats to high intensity light (LD). We evaluated the retinal function, and we performed morphological and molecular analysis a week after the LD, in accordance with the well-established protocol of our light damage model.

Results: DPSCs-CM obtained from hypoxia or normoxia, were able to preserve the retinal function, to reduce microglial activation and their migration toward outer nuclear layer (ONL). Furthermore, we demonstrated that the treatment with normoxic DPSCs-CM limited the hot spot extension and preserved the ONL thickness better than the hypoxic DPSCs-CM. The different concentrations of growth factors and cytokines detected in both CM played a key role in the understanding of the greatest protective effect of the normoxic-CM compared to hypoxic-CM.

Conclusions: Taken together, our study demonstrated that normoxic DPSCs-CM represents an eligible candidate to counteract retinal degeneration and, therefore, a promising therapeutic agent for AMD.