Evaluating the neuroprotective potential of MSC secretome for retinal neurodegenerative diseases

Retinal neurodegenerative diseases (RND), including age‐related macular degeneration, glaucoma, diabetic retinopathy, retinitis pigmentosa, and others, are the most common cause of irreversible low vision and blindness. Although the aetiology and clinical characteristics of retinal RND can differ phenotypically, the neurodegenerative mechanisms of these diseases share common cellular and molecular signalization pathways. No cures are available for most RND, and cell‐based therapy may be a potential treatment through the paracrine properties of mesenchymal stromal cells (MSC). Furthermore, developing cell‐free compositions based on the production of “MSC secretome cocktails” is a promising therapeutic strategy and has significant advantages over using living cells in clinical practice. Ex vivo neuroretina models are adequate tools for evaluating retinal physiology and pathobiology. Neuroretina explant cultures closely resemble in vivo conditions, thus, preserving complex in vivo neuronal connections and retaining the functionality of non‐neuronal cells of the retina. Furthermore, cellular and molecular biology techniques can be applied to retinal explant cultures. In the ex vivo spontaneous neuroretinal degeneration model, the MSC secretome preserves retinal morphology and limits pro‐apoptotic‐ and pro‐necroptotic‐related genes and protein expression. Furthermore, the MSC secretome modulates autophagy‐related genes and proteins and stimulates the activation of antioxidant‐associated genes. Therefore, the neuroprotective ability of the MSC secretome is associated with the inhibition of apoptosis and necroptosis, modulation of autophagy, and activation of the antioxidant machinery during retinal degeneration. MSC secretome shows neuroprotective properties and the potential to modulate retinal responses to neurodegeneration, thus reinforcing the idea that MSC secretome may be a therapeutic strategy for treating RND.