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

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. To date, there are no effective therapies to counteract AMD towards the most severe stages characterised by a progressive loss of photoreceptors triggered by retinal pigmented epithelium dysfunction. Given their easy source and their high proliferative potential, Dental Pulp Stem Cells (DPSCs) are considered promising for regenerative medicine. The main advantage of DPSCs is related to their paracrine immunosuppressive and immunoregulatory abilities, including the capability to promote regeneration of damaged tissues. Recent studies demonstrated the therapeutic potential of DPSCs-conditioned media (CM) in neurodegenerative diseases. In addition, we have already shown a differential expression of some growth factors and cytokines in CM derived from DPSCs cultured in hypoxia and normoxia conditions. In this study we evaluated the capability of DPSCs-CM to counteract retinal degeneration in an animal model of AMD. 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. DPSCs-CM obtained from hypoxia (HYPO-CM) or normoxia (NORM-CM), were able to preserve the retinal function, to reduce the damaged area and to counteract the upregulation of key factors involved in retinal degeneration, like FGF-2. Furthermore, we demonstrated that neither conditioned media modified inflammatory activation, as shown by both microglia activation and GFAP upregulation, but in vitro studies demonstrated a significant effect of both CM to counteract oxidative stress, one of the main causes of AMD. Taken together, our study demonstrated that NORM-CM and HYPO-CM, albeit with a different chemical composition, could represent eligible candidates to counteract retinal degeneration in an animal model of AMD. Further studies are needed to obtain conditioned media with the best performance in term of retinal protection. • Oxidative stress is the main cause of vision loss in Age-related Macular Degeneration. • The secretome released in normoxia and hypoxia conditions by DPSCs counteracts retinal degeneration. • NORM-CM and HYPO-CM from DPSCs maintain retinal morphology and function in vivo model of Age-related Macular Degeneration. • NORM-CM and HYPO-CM counteract oxidative stress reducing Reactive Oxygen Species in retinal epithelial cells exposed to H 2 O 2 .