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Emily Mathieu, Neeru Gupta, Maryam Firas, Yeni H Yucel; In vivo evidence of tracer movement from the cerebrospinal fluid into the eye in mice. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Preliminary evidence suggests there may be communication between the cerebrospinal fluid (CSF) and eye1, however these findings have yet to be confirmed in vivo in an animal model. The purpose of this study was to determine whether tracers injected into the CSF move into the eye in mice.
Under general ketamine/xylazine anesthesia, male CD1 mice (n=4) were placed in a stereotaxic frame, a suboccipital incision was made, and 3 μL of a near-infrared tracer (IRDye 800, LI-COR, NE, USA) was injected into the CSF of the cisterna magna. Tracer was either carboxylated (1 kDa; n=2), or conjugated to 7.5 kDa polyethylene glycol (PEG; n=2). After dilation with topical tropicamide 1% (Alcon, Canada), a Spectralis HRA-2+OCT scanning laser ophthalmoscope (Heidelberg Engineering, Germany) was used to capture infrared reflectance and infrared fluorescence fundus images before and at regular intervals following CSF injection. Animals were sacrificed 30 minutes (n=1), 90 minutes (n=2), or 3 hours (n=1) after tracer injection.
Near-infrared fluorescent tracer was observed in all eyes within 21 minutes after injection in the CSF. A vascular pattern emanating from the optic nerve head was noted in all cases and a halo of fluorescent signal was seen in the peripapillary retina, which spread peripherally with time (Fig. 1). Following CSF injection, carboxylated IRDye appeared within the eye earlier than PEGylated IRDye (7-15 minutes vs. 18-21 minutes). Signal in the eye persisted for up to 3 hours.
The appearance of tracers within the posterior segment of the eye shortly after CSF injection provides evidence of a direct communication between these fluid compartments. Further studies are needed to explore the exact nature of the pathway, and its potential role in ocular health and disease.1Mathieu et al. “Does Cerebrospinal Fluid Communicate with the Eye?” Poster presented at: ARVO Annual Meeting; 2013, May 5-9; Seattle, WA.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
Figure 1. Near-infrared fluorescence time-course images of mouse fundus following cerebrospinal fluid injection of carboxylated IRDye 800.
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