Abstract
Bone marrow-derived cells have been used in different animal models of neurological diseases. We investigated the therapeutic potential of mesenchymal stem cells (MSC) injected into the vitreous body in a model of optic nerve injury. Adult (3–5 months old) Lister Hooded rats underwent unilateral optic nerve crush followed by injection of MSC or the vehicle into the vitreous body. Before they were injected, MSC were labeled with a fluorescent dye or with superparamagnetic iron oxide nanoparticles, which allowed us to track the cells in vivo by magnetic resonance imaging. Sixteen and 28 days after injury, the survival of retinal ganglion cells was evaluated by assessing the number of Tuj1- or Brn3a-positive cells in flat-mounted retinas, and optic nerve regeneration was investigated after anterograde labeling of the optic axons with cholera toxin B conjugated to Alexa 488. Transplanted MSC remained in the vitreous body and were found in the eye for several weeks. Cell therapy significantly increased the number of Tuj1- and Brn3a-positive cells in the retina and the number of axons distal to the crush site at 16 and 28 days after optic nerve crush, although the RGC number decreased over time. MSC therapy was associated with an increase in the FGF-2 expression in the retinal ganglion cells layer, suggesting a beneficial outcome mediated by trophic factors. Interleukin-1β expression was also increased by MSC transplantation. In summary, MSC protected RGC and stimulated axon regeneration after optic nerve crush. The long period when the transplanted cells remained in the eye may account for the effect observed. However, further studies are needed to overcome eventually undesirable consequences of MSC transplantation and to potentiate the beneficial ones in order to sustain the neuroprotective effect overtime.
Highlights
Diseases that affect the optic nerve, such as glaucoma and diabetic retinopathy, are common causes of blindness worldwide [1]
mesenchymal stem cells (MSC) were labeled with superparamagnetic iron oxide nanoparticles (SPION) (FeraTrack), which can be visualized in vivo by magnetic resonance imaging (MRI) and ex vivo by histochemical methods in the ocular tissues
IBA1 was expressed in the inner retinal layers, probably by resident microglia, but the vast majority of the cells found in the vitreous body were negative to IBA1 (Figure S2 in File S1)
Summary
Diseases that affect the optic nerve, such as glaucoma and diabetic retinopathy, are common causes of blindness worldwide [1]. In mammals, injury to the optic nerve, e.g., crush or transection, results in the progressive retrograde degeneration of axons and the death of retinal ganglion cells (RGC), mainly by apoptosis [3,4,5]. Strategies developed to enhance survival and regeneration of RGC include the inhibition of myelin-derived proteins and blockage of rho kinase [6,7,8,9], deletion of PTEN [10] and/or SOCS-3 [11,12], macrophage activation and delivery of oncomodulin [13,14,15,16,17,18], delivery and stimulation of ciliary neurotrophic factor [8,19,20], regulation of KLF family members [21], cell therapy [22,23,24] and a combination of multiple approaches [14,25]. Injection of trophic factors into the vitreous body prevents neuronal loss, but the effect is transitory [26], and even after peripheral-nerve grafting, which provides a permissive environment for regeneration of central neurons, RGC survival decreases overtime [27]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
