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V. Lee, M. Dutt, K. S. Shindler; Histologic Correlation of Retinal Ganglion Cell Loss to Optical Coherence Tomography and Optokinetic Response in Murine Model of Optic Nerve Crush. Invest. Ophthalmol. Vis. Sci. 2010;51(13):639.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the utility of a commercially available mouse Optical Coherence Tomography (OCT) for detecting loss of retinal ganglion cell (RGC) axons following optic nerve crush injury, and compare observed structural changes to visual function measured by optokinetic responses (OKR).
C57/Bl6 mice underwent optic nerve crush of the left eyes, while the right eyes served as controls. RGCs were retrogradely labeled with fluorogold by injection into the superior colliculi one week prior. Circumpapillary OCT and OKR measurements were obtained at baseline, and weekly thereafter for three weeks. At the end of the three week period, eyes from half the mice were removed and processed for routine histologic evaluation. Retinas were isolated from the remaining eyes, and RGCs were counted by fluorescent microscopy.
A significant decrease in vision, marked by reduced OKR, was observed in the left eyes following optic nerve crush as compared to baseline or to the right (control) eyes. This decreased vision corresponded with structural loss of RGCs, as the average number of RGCs were significantly decreased in left eyes compared to right eyes. In a few individual mice, progressive retinal nerve fiber layer (RNFL) thinning was detected by OCT in the left eye over the three week course. However, due to intervariability between mice, the overall measurements were inconclusive, as the average RNFL thickness measured by OCT did not demonstrate a statistically significant difference between right and left eyes.
Decreased OKR measurements following optic nerve crush in mice correlate with loss of RGCs, and suggest this method can be used to estimate decreased visual function following nerve injury. Current commercially available mouse OCT may not be sensitive enough to detect significant changes in RNFL thickness secondary to optic nerve crush, although clear progressive loss seen in some animals suggests that significant differences might be seen in larger cohorts of mice.
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