MSC exosomes and MSC exosomes loaded with LncRNA H19 as nanotherapeutics regulate the neurogenetic potential of Müller Glial Cells in dry age-related macular degeneration

In retinal degeneration diseases such as dry age-related macular degeneration (AMD), Müller Glial Cells (MGCs) in mammals undergo a process of reactive gliosis leading to the progression of dry AMD. Here, It is demonstrated that exosomes derived from mesenchymal stem cells (MSC exosomes) and MSC exosomes loaded with LncRNA H19, acting as nanotherapeutics, can be regulated by MGCs in dry AMD. In the in vivo study, MSC exosomes were administered via intravitreal injection. MSC exosomes effectively redirected MGCs from gliosis to dedifferentiation and alleviated MGCs-to-epithelial transition by inhibiting oxidative stress in mice with dry AMD induced by NaIO₃. In the in vitro study, MSC exosomes promoted MGCs dedifferentiation by activating Wnt/β-catenin signaling pathway and prevented oxidative stress-induced MGCs gliosis and MGCs-to-epithelial transition by inhibiting TGFβ1 signaling pathway. MSC exosomes loaded with LncRNA H19 enhanced the activation of Wnt/β-catenin signaling pathway and the inhibition of the TGFβ1 signaling pathway compared with MSC exosomes. These results suggest that MSC exosomes regulate the neurogenetic potential of MGCs by redirecting MGCs from gliosis to dedifferentiation and alleviating the transformation of MGCs to epithelial cells through regulating oxidative stress. Regulating LncRNA H19 in MGCs to promote mammalian retinal regeneration in dry AMD was suggested for the first time.

Dry age-related macular degeneration; LncRNA H19; MSC exosomes; MSCs; Müller glial cells; Oxidative stress; Retinal regeneration.