July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Adrenergic Control of Lymphatic Drainage from the Eye
Author Affiliations & Notes
  • Joseph Hanna
    Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada
    Departments of Ophthalmology and Vision Sciences, and Laboratory Medicine and Pathobiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
  • Yeni H Yucel
    Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada
    Departments of Ophthalmology and Vision Sciences, and Laboratory Medicine and Pathobiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
  • Xun Zhou
    Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada
  • Nayeon Kim
    Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada
  • Neeru Gupta
    Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada
    Departments of Ophthalmology and Vision Sciences, and Laboratory Medicine and Pathobiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
  • Footnotes
    Commercial Relationships   Joseph Hanna, None; Yeni Yucel, None; Xun Zhou, None; Nayeon Kim, None; Neeru Gupta, None
  • Footnotes
    Support  Canadian Institutes of Health Research (YY, NG), Canada Foundation for Innovation (YY), Glaucoma Research Society of Canada (NG, YY), Henry Farrugia Research Fund (YY), Thor and Nicky Eaton Research Fund (NG), Vision Science Research Program (JH) and the Ontario Graduate Scholarship (JH).
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6472. doi:
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    • Get Citation

      Joseph Hanna, Yeni H Yucel, Xun Zhou, Nayeon Kim, Neeru Gupta; Adrenergic Control of Lymphatic Drainage from the Eye. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6472.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : We have recently described a noninvasive method to quantify the lymphatic drainage from the eye, the third outflow pathway of the aqueous humor (Yucel et al., 2018). To date, the effect of glaucoma drugs on this pathway have not been explored and here we assess the effects of timolol and brimonidine, two widely used adrenergic glaucoma drugs, on ocular lymphatic drainage.

Methods : Wild-type CD1 mice were treated with topical timolol 0.5%, a ß-adrenergic blocker, (n=4; 10μL; Sandoz) or artificial tears (n=5; 10μL; Alcon) to the right eye twice at 9 pm and 9 am next morning. In a second set, mice were treated with topical brimonidine 0.15%, an α2-adrenergic agonist, (n=8; 10μL; Allergan) or artificial tears (n=6; 10μL) to the right eye twice at 5 pm and 9 am next morning. In both experiments, intraocular pressure of treated eyes measured by tonometry was significantly lowered (p<0.05). One hour after the last dose, QC-1 quencher dye (1μL; 1mM; Li-Cor) conjugated to bovine serum albumin was injected intracamerally into the right eye. In vivo photoacoustic tomography (MSOT, iThera Medical) of the head and neck was performed before injection and at 20 minutes, 2 and 4 hours after injection. Right neck lymph nodes were outlined, and QC-1 signal intensity was measured using ViewMSOT software, and signal intensity slopes and area under the curve (AUC) were calculated. Treated-mice were compared with controls using t-test and p<0.05 was considered as statistically significant.

Results : In the timolol study, the tracer signal in the right neck lymph node increased steadily over 4 hours in both treated mice and controls. The mean slope of right neck lymph node signal in controls was significantly steeper compared to timolol-treated group (p= 0.03). Controls also showed a significantly greater AUC compared to the timolol-treated group (p= 0.03). In the brimonidine study, the tracer signal in the right neck lymph node increased steadily and the mean slope in treated mice was significantly steeper compared to controls (p= 0.02). The AUC in the brimonidine-treated mice was also greater compared to controls (p= 0.04).

Conclusions : This is the first study to quantify in vivo the effect of a drug on ocular lymphatic drainage. The findings that timolol reduces lymphatic outflow and that brimonidine increases it may be relevant for management of glaucoma. Further studies are needed to understand the pharmacological determinants of ocular lymphatic drainage.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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