Lymphatics in Eye Fluid Homeostasis: Minor Contributors or Significant Actors?

Lymphatic vessels exert major effects on the maintenance of interstitial fluid homeostasis, immune cell trafficking, lipid absorption, tumor progression and metastasis. Recently, novel functional roles for the lymphatic vasculature have emerged, which can be associated with pathological situations. Among them, lymphatics have been proposed to participate in eye aqueous humor drainage, with potential consequences on intraocular pressure, a main risk factor for progression of glaucoma disease. In this review, after the description of eye fluid dynamics, we provide an update on the data concerning the distribution of ocular lymphatics. Particular attention is given to the results of investigations allowing the three dimensional visualization of the ocular surface vasculature, and to the molecular mechanisms that have been characterized to regulate ocular lymphatic vessel development. The studies concerning the potential role of lymphatics in aqueous humor outflow are reported and discussed. We also considered the novel studies mentioning the existence of an ocular glymphatic system which may have, in connection with lymphatics, important repercussions in retinal clearance and in diseases affecting the eye posterior segment. Some remaining unsolved questions and new directions to explore are proposed to improve the knowledge about both lymphatic and glymphatic system interactions with eye fluid homeostasis.