Abstract
Glaucoma surgeries, such as trabeculectomy, are performed to lower intraocular pressure to reduce risk of vision loss. These surgeries create a new passage in the eye that reroutes the aqueous humor outflow to the subconjunctival space, where the fluid is presumably absorbed by the conjunctival lymphatics. Here, we characterized the development and function of the ocular lymphatics using transgenic lymphatic reporter mice and rats. We found that the limbal and conjunctival lymphatic networks are progressively formed from a primary lymphatic vessel that grows from the nasal-side medial canthus region at birth. This primary lymphatic vessel immediately branches out, invades the limbus and conjunctiva, and bidirectionally encircles the cornea. As a result, the distribution of the ocular lymphatics is significantly polarized toward the nasal side, and the limbal lymphatics are directly connected to the conjunctival lymphatics. New lymphatic sprouts are produced mainly from the nasal-side limbal lymphatics, posing the nasal side of the eye as more responsive to fluid drainage and inflammatory stimuli. Consistent with this polarized distribution of the ocular lymphatics, a higher drainage efficiency was observed in the nasal side than the temporal side of the eye when injected with a fluorescent tracer. In contrast, blood vessels are evenly distributed at the anterior surface of the eyes. Also, we found that these distinct vascular distribution patterns were conserved in human eyes. Together, our study demonstrated that the ocular surface lymphatics are more densely present in the nasal side and uncovered the potential clinical benefits in selecting the nasal side as a glaucoma surgery site to improve fluid drainage.
Highlights
The lymphatic system controls interstitial fluid homeostasis, serves as conduits for immune cell trafficking, and absorbs dietary fat and large molecules in the digestive system [1, 2]
The distribution of the ocular lymphatics is significantly polarized toward the nasal side, and the limbal lymphatics are directly connected to the conjunctival lymphatics
prospero homeobox 1 (Prox1) was strongly expressed in both the inner and outer walls of Schlemm’s canal. It has not been reported whether the limbal lymphatics harbor the luminal valves, a hallmark of collecting lymphatics, and how they extend beyond the limbus area
Summary
The lymphatic system controls interstitial fluid homeostasis, serves as conduits for immune cell trafficking, and absorbs dietary fat and large molecules in the digestive system [1, 2]. Dysfunctional, damaged, and/or malformed lymphatic vessels cause abnormal interstitial fluid accumulation, which leads to interstitial pressure buildup and results in tissue swelling. Many pathological conditions, such as brain injuries, glaucoma, and lymphedema, are known to be associated with increased interstitial pressure. While the lymphatics serve as the primary drainage route in most tissues and organs, fluid homeostasis in the eyes is controlled by 2 fluid-draining systems.
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