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Chendong Pan, Anna M Demetriades; Topical delivery of NT4 promotes retinal ganglion cell survival following neuronal injury in Thy1.YFP mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5638.
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© ARVO (1962-2015); The Authors (2016-present)
Neurotrophin-4 (NT4) is a neurotrophic factor that regulates the survival, differentiation and mature function of neurons. This study aims to determine if topical delivery of NT4 promotes retinal ganglion cell survival in a murine model of optic nerve crush injury.
Adult Thy1.YFP mice, which express yellow fluorescent protein as a marker of viable retinal neurons, were used for the purpose of this study. At the time of optic nerve crush injury, an ophthalmic gel-forming solution containing purified NT4 (10µg/µl) was applied to the eye on a daily basis. Micron III fundus imaging was performed to quantify in vivo retinal ganglion cell fluorescence during this time. Mice were sacrificed at four days and retinal flat mounts prepared. ELISA was performed to quantify NT4 levels in the retina and optic nerve of treated eyes.
Topical delivery of NT4 resulted in increased NT4 levels (ng/mg protein) in the retina compared to untreated eyes (2.4 vs 0.01) and optic nerve (105.2 vs 0.1) (n=5). Micron III image fluorescence analysis demonstrated that the majority of RGC loss (78% fluorescence peak loss) occurred within the first four days of optic nerve crush injury. A reduction in RGC loss (49% fluorescence peak loss) was observed following topical delivery of NT4 at four days. In retinal flatmounts, the number of fluorescent cells in untreated eyes without optic nerve crush injury was 3213±95 cells/mm3. At four days following optic nerve crush injury, NT4 treated eyes (2153± 174, n=8) showed significantly more remaining fluorescent cells than untreated eyes (1496±82, n=4) (p<0.0001).
Topical delivery of NT4 results in increased NT4 levels in the retina and optic nerve leading to protection of retinal neurons following optic nerve crush injury in Thy1-YFP mice. Fluorescent cells predominantly represent retinal ganglion cells in this model; therefore these findings suggest that topical NT4 provides a neuroprotective effect on retinal ganglion cells in the immediate period following optic nerve injury.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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