title: A model to measure lymphatic drainage from the eye.
abstract: Intraocular pressure (IOP) is the most important risk factor for glaucoma development and progression. Most anti-glaucoma treatments aim to lower IOP by enhancing aqueous humor drainage from the eye. Aqueous humor drainage occurs via well-characterized trabecular meshwork (TM) and uveoscleral (UVS) pathways, and recently described ciliary body lymphatics. The relative contribution of the lymphatic pathway to aqueous drainage is not known. We developed a sheep model to quantitatively assess lymphatic drainage along with TM and UVS outflows. This study describes that model and presents our initial findings. Following intracameral injection of (125)I-bovine serum albumin (BSA), lymph was continuously collected via cannulated cervical lymphatic vessels and the thoracic lymphatic duct over either a 3-h or 5-h time period. In the same animals, blood samples were collected from the right jugular vein every 15 min. Lymphatic and TM drainage were quantitatively assessed by measuring (125)I-BSA in lymph and plasma, respectively. Radioactive tracer levels were also measured in UVS and "other" ocular tissue, as well as periocular tissue harvested 3 and 5 h post-injection. Tracer recovered from UVS tissue was used to estimate UVS drainage. The amount of (125)I-BSA recovered from different fluid and tissue compartments was expressed as a percentage of total recovered tracer. Three hours after tracer injection, percentage of tracer recovered in lymph and plasma was 1.64% ± 0.89% and 68.86% ± 9.27%, respectively (n = 8). The percentage of tracer in UVS, other ocular and periocular tissues was 19.87% ± 5.59%, 4.30% ± 3.31% and 5.32% ± 2.46%, respectively. At 5 h (n = 2), lymphatic drainage was increased (6.40% and 4.96% vs. 1.64%). On the other hand, the percentage of tracer recovered from UVS and other ocular tissue had decreased, and the percentage from periocular tissue showed no change. Lymphatic drainage increased steadily over the 3 h post-injection period, while TM drainage increased rapidly - reaching a plateau at 30 min. This quantitative sheep model enables assessment of relative contributions of lymphatic drainage, TM and UVS outflows, and may help to better understand the effects of glaucoma agents on outflow pathways.
authors.affiliation: Department of Ophthalmology & Vision Sciences, University of Toronto, St. Michael's Hospital, Canada.
authors.forename: Minhui
authors.initials: M
authors.lastname: Kim
authors.forename: Miles G
authors.initials: MG
authors.lastname: Johnston
authors.forename: Neeru
authors.initials: N
authors.lastname: Gupta
authors.forename: Sara
authors.initials: S
authors.lastname: Moore
authors.forename: Yeni H
authors.initials: YH
authors.lastname: Yücel
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000502:physiology*; D007429:Intraocular Pressure / Q000502:physiology; D008196:Lymph / Q000502:physiology*; D008208:Lymphatic System / Q000502:physiology*; D042601:Lymphatic Vessels / Q000378:metabolism; D023421:Models, Animal; D012590:Sclera / Q000378:metabolism*; D012711:Serum Albumin, Radio-Iodinated; D012756:Sheep; D014065:Tonometry, Ocular; D014129:Trabecular Meshwork / Q000378:metabolism*; D014602:Uvea / Q000378:metabolism*
chemical_list: D012711:Serum Albumin, Radio-Iodinated