A model to measure lymphatic drainage from the eye

Area of Science:

• Ophthalmology and Vision Science
• Fluid Dynamics in Biological Systems
• Animal Models for Disease Research

Background:

• Intraocular pressure (IOP) is a primary risk factor for glaucoma.
• Current anti-glaucoma treatments focus on enhancing aqueous humor outflow via trabecular meshwork (TM) and uveoscleral (UVS) pathways.
• The role of recently identified ciliary body lymphatics in aqueous humor drainage remains unclear.

Purpose of the Study:

• To develop and validate a quantitative sheep model for assessing aqueous humor drainage.
• To simultaneously evaluate drainage contributions from lymphatic, TM, and UVS pathways.
• To provide insights into the relative importance of these outflow routes.

Main Methods:

• Intracameral injection of a radioactive tracer ((125)I-bovine serum albumin) in sheep.
• Continuous collection of lymph from cannulated cervical lymphatic vessels and thoracic duct.
• Measurement of tracer in lymph, plasma (for TM outflow), UVS tissue, and other ocular/periocular tissues at 3 and 5 hours post-injection.

Main Results:

• At 3 hours, tracer recovery was 1.64% in lymph, 68.86% in plasma (TM outflow), and 19.87% in UVS tissue.
• Lymphatic drainage showed a steady increase over 3 hours, while TM drainage plateaued by 30 minutes.
• At 5 hours, lymphatic drainage increased, whereas UVS and other ocular tissue drainage decreased.

Conclusions:

• The developed sheep model effectively quantifies contributions of lymphatic, TM, and UVS aqueous humor outflow pathways.
• Lymphatic drainage plays a significant, time-dependent role in aqueous humor outflow.
• This model can aid in understanding the mechanisms of glaucoma and evaluating novel therapeutic agents targeting outflow pathways.