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Shaomei Wang, YuChun Tsai, Benjamin Bakondi, Sergey Girman, Lin Shen, Bin Lu; Systemic administration of MSCs preserves RGC survival after optic nerve crush. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2440.
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Traumatic optical neuropathy (TON) results from trauma to optic nerves by head and eye injuries to both military and civilian population such as accidents, recreation 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. Here we used systemic administration of bone marrow derived mesenchymal stem cells (MSCs) to treat TON in a well-established rat model-optic nerve crush (ONC).
Long Evans rats, both sex at 6-12 weeks old were used for creating ONC model (one side) with customized forceps. On the next day, 2millions of MSCs-derived from Long Evans rats were injected via tail vein. Visual function was tested by optokinetic response, luminance threshold recording from the superior colliculus and electroretinograph at 8 and 14 days after ONC. Survival retinal ganglion cells (RGCs) were quantified by applying fluorogold to the superior colliculus and antibody-Brn3 staining on retinal whole-mount preparation. Optic nerve axons were examined by injecting CTb intravenously and antibody-RT97 staining. Stereology was used to count the number of RGC survival.
There was about 60% RGC survived in animals with intravenous injection of MSCs after ONC, compared with 40% RGC survival in control animals (no treatment after ONC). This difference is significant (p<0.05). The visual acuity was also preserved in MSC treated animals compared with control. Luminance threshold recordings revealed there was no signal detected after ONC, indicating the integrity of retina is required for luminance threshold recording. On all the MSC treated animals, there were some RGC axons regeneration, future manipulations to enhance axons grow is needed.
Systemic administration of allogeneic MSCs promotes RGC survival and enhances RGC axon regeneration after optic nerve crush. Long-term study using this approach to preserve both RGC and its axons is under investigation.
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