Non-Invasive Cell-Based Therapy for Traumatic Optic Neuropathy

Abstract

Abstract : Traumatic optical neuropathy (TON) results from trauma to optic nerve by head and eye injuries to both military and civilian population such as accidents, and blast related combat trauma. TON leads to irreversible blindness and represent a major public health burden with both economical and social impacts. Unfortunately, treatment is still rather limited. A large body of evidence indicates that TON affects optic nerve and its target neurons in the central nervous system, which provide vital retrograde trophic support to optic nerve. We hypothesize that systemic administration of bone marrow derived mesenchymal stem cells (MSC) to treat traumatic optic neuropathy (TON) will preserve/repair optic nerve, stabilize the unstable environment due to trauma and promote RGC regeneration and outgrowth by promoting the release of paracrine and autocrine mediators; induced Schwann cells from MSC (M-Sch) will repair the damaged RGC by remyelinating and providing multiple trophic factors. Previous studies have shown that activation in retinoic acid (RA) signalling triggers neurite outgrowth in adult mice. Here we found that intravitreal injection of retinoid X receptor agonist SR11237 not only preserved RGCs, and promoted RGC axon outgrowth at both 8 days and 14 days after TON. We have used Long Evan (LE) rats as a model for TON, MSC were isolated from LE rats, M-Sch were induced from MSC. Our main findings: (a) Using our modified forceps, a reliable and reproducible TON model was created. (b) Rat MSC and M-Sch were reliable produced for experiments. (c) Systemic administration of MSCs significantly preserved retinal ganglion cell survival after TON. (d) Systemic administration of MSCs also promote limited RGC axons regeneration. (e) Intravitreal injection of retinoid X receptor agonist SR11237 also protect RGC survival after TON and promote RGC regeneration. (f) Systemic administration of MSCs induced up expression of trophic factors in the retina (CNTF, BDN