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Akshay Gurdita, Jacek M Kwiecien, Vivian Choh; Subdural infusion of kynurenic acid causes myelin loss in chicken optic nerves. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1740. doi: https://doi.org/.
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Kynurenic acid (KYNA) is a neuro-active metabolite of tryptophan present in the central nervous system. Previous work revealed that prolonged subdural infusion of high levels of KYNA reduced the numbers of myelin sheaths in the rat spinal cord without inducing an inflammatory response. We hypothesize that a similar infusion of kynurenic acid (KYNA) induces myelin loss in the optic nerves of chickens.
Seven day old gallus gallus domesticus chickens were randomly selected for infusion of 50 mM KYNA (n = 2) or phosphate buffered saline (PBS; n = 3), at a rate of 0.5 mL/hr. KYNA or PBS were loaded into an osmotic pump that was attached to a catheter. The catheter was inserted into the optic nerve and the pump was implanted under the skin in upper back region of the bird. A third group of birds received no treatment (n = 4) and served as negative controls. After 7 days of infusion, birds were sacrificed by cardiac perfusion with Karnovsky fixative. Negative controls were perfused at the same age as the infused chicks. Optic nerves were dissected and embedded in epon/araldite resin. Electron micrographs were collected and the percentage of myelinated axons were averaged from 0.01 mm2 areas within 4 quadrants of the optic nerve. A one-way ANOVA was used to determine differences between the groups.
KYNA-infused nerves exhibited widespread loss of myelin sheaths associated with astrogliosis and without inflammatory infiltration of the nerve. PBS-infused nerves exhibited slight localised loss of myelin sheaths while all the nerves in the negative control birds had no changes. Preliminary data for the implanted nerves from each group indicated that the percent of myelinated axons in KYNA-infused chicks (mean ± sd: 11.4% ± 1.5%) were lower than the PBS-infused (72.8% ± 11.0%; p = 0.0004) and negative control birds (90.0% ± 4.10; p = 0.0002). The percent of myelinated axons in PBS-infused birds, were slightly reduced compared to negative control birds (p = 0.0401).
Subdural infusion of 50 mM KYNA for 7 days induces myelin loss without inflammatory infiltration in the chicken optic nerve. PBS-infused birds also showed a slight loss of myelination, likely due to the surgical procedure. Our model of subdural infusion of KYNA may be useful for illuminating mechanisms of oligodendrocyte function and myelination in the optic nerve.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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