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Kirsten Cardinell, Yeni H Yucel, Xun Zhou, Neeru Gupta; Non-invasive in vivo mapping of aqueous outflow and lymphatic drainage from the eye. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3769.
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The purpose of this study is to non-invasively map aqueous outflow and lymphatic drainage from the eye in vivo.
Tracer dye called QC-1 absorbs light in the near infrared range, and was used to track aqueous humour movement. Photoacoustic tomography (PAT), a light and sound based imaging technology, was used to track QC-1 in vivo. For in vitro imaging, agar phantoms were generated using 10 serial dilutions of QC-1. For in vivo imaging, 0.5µL Bovine Serum Albumin (10mg/mL; Sigma-Aldrich, USA) conjugated with IRDye QC-1 (LI-COR, USA) was injected intracamerally into the right eye of 9 CD-1 mice under general anesthesia. Mice were scanned using PAT (MSOT inVision 128, iThera Medical, Germany). Cross-sectional imaging of the head and neck (150 μm; 0.5 mm steps) at wavelengths from 680 to 900 nm before and 10 min, 1 hr, 2 hrs, 4 hrs, and 6 hrs after injection. MSOT software was used to reconstruct and detect QC-1 signal. The mean pixel intensity was measured in both eyes and cervical lymph nodes. The slope of change in normalized mean pixel intensity from 10 min to 6 hrs was calculated for each region of interest. The difference in slopes at 2.5 hrs between eyes (n=9) was compared using t-test. A similar analysis was performed for in 4 mice with detectable signal in nodes.
Phantoms showed a linear relationship between QC-1 dye concentration and photoacoustic signal. Strong QC-1 signal was detected in the right eye of all mice (n=9) (Fig1A). Decreasing QC-1 signal was observed at 1 h, 2 hrs, 4 hrs and 6 hrs (Fig1B). QC-1 signal in right cervical nodes was seen at 2 hrs after injection with a peak at 4 hrs (n=4)(Fig1C). No QC-1 signal was detected in the left eye and left cervical nodes. Slope differences at 2.5 hr between right and left eyes was significant (n=9; P<0.01), as was the difference between right and left nodes (n=4; P= 0.01).
This is the first study to assess outflow and lymphatic drainage in vivo in the infrared range. Further studies to quantify the photoacoustic signal will help to understand outflow in the normal eye and in response to glaucoma drugs.Acknowledgments: CIHR, CFI, Henry Farrugia and Nicky & Thor Eaton Research Funds.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
Fig 1 2 hrs after intracameral injection, QC-1 signal is seen in the right eye and cervical node.
Fig 2A and Fig 2B show QC-1 signal intensity in eyes (n=9) and nodes (n=4) over time.
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