Mesenchymal stem cell therapy for retinal ganglion cell neuroprotection and axon regeneration

Retinal ganglion cells (RGCs) are responsible for propagating signals derived from visual stimuli in the eye to the brain, along their axons within the optic nerve to the superior colliculus, lateral geniculate nucleus and visual cortex of the brain. Damage to the optic nerve either through trauma, such as head injury, or degenerative disease, such as glaucoma causes irreversible loss of function through degeneration of non-regenerating RGC axons and death of irreplaceable RGCs, ultimately leading to blindness (Berry et al., 2008). The degeneration of RGCs and their axons is due to the loss of the necessary source of retrogradely transported neurotrophic factors (NTFs) being hindered by axonal injury. NTFs are survival factors for neurons and play a pivotal part in axon regeneration. Stem cells particularly mesenchymal stem cells (MSCs) have been shown to possess a natural intrinsic capacity for paracrine support, releasing multiple signalling molecules including NTFs. By transplanting MSCs into the vitreous, they are positioned adjacent to the injured retina to provide paracrine-mediated therapy for the retinal neuronal cells (Johnson et al., 2010a; Mead et al., 2013). Additionally, MSCs may be pre-differentiated into supportive glial-like cells, such as Schwann cells, which could further increase their potential for paracrine support of injured neurons (Martens et al., 2013). Thus, MSCs have received considerable attention as a new cellular therapy for both traumatic and degenerative eye disease, acting as an alternative source of NTFs, protecting injured RGCs and promoting regeneration of their axons