Editors Selection IGR 21-2

Basic Science: Is lymphatic drainage decline linked to age-related eye disease?

Alex Huang
Jong Yeon Lee

Comment by Alex Huang & Jong Yeon Lee on:

86629 Age-related decline of lymphatic drainage from the eye: A noninvasive in vivo photoacoustic tomography study, Yücel YH; Cheng F; Cardinell K et al., Experimental Eye Research, 2020; 194: 108029

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The authors of this paper previously described the presence of intraocular luminal pathways expressing lymphatic markers in the uveal tract1 as well as a photoacoustic method2 to follow lymphatic delivery of intraocular injected tracer (QC1:albumin). Here, the authors use mice and nicely demonstrate ~64% reduced delivery of intraocular injected QC1:albumin to ipsilateral cervical lymph nodes of older (~13.5 months; n = 13) compared to younger (~2.5 months; n = 10) mice. While the photoacoustic imaging is described as non-invasive, this overall approach is still invasive as the tracer must be directly injected into the anterior chamber of the eyes.

The mechanism of what is happening is of great interest. Uveoscleral outflow is longknown to be decreased with age.3 The authors described the uveolymphatic pathway, and this pathway may share initial portions with the uveoscleral outflow pathway. Thus, any common age-related outflow decrease in these two pathways may help localize age-related changes to the shared proximal portions. Alternatively, these findings could be due to age-related changes in distal lymphatic outflow along the cervical chain leading to the lymph nodes themselves. Lastly, some tracer could have also moved through conventional outflow, leaked out, and been picked up by the subconjunctival lymphatics as another way for intraocular QC1:albumin to reach cervical lymph nodes. Age-related changes here could be relevant as well.

Overall, ocular lymphatic biology in the eye is a rapidly growing area of research. Lymphatics in the conjunctiva,4 cornea (post-stimulatory), and intraocular likely play a role in fluid homeostasis and immune surveillance. Even Schlemm's canal has a partial molecular lymphatic identity.5 Thus, potential clinical benefit exists for the future. Promotion of lymphatic pathways could improve native aqueous humor outflow or outflow after glaucoma surgery. Alternatively, limiting lymphatics could assist in developing better drug delivery solutions for the eye. What is clear at this point is that to achieve all of this requires considerably more research into the structure and function of ocular lymphatics.

Promotion of lymphatic pathways could improve native aqueous humor outflow or outflow after glaucoma surgery.


  1. Yucel YH, Johnston MG, Ly T, et al. Identification of lymphatics in the ciliary body of the human eye: a novel "uveolymphatic" outflow pathway. Exp Eye Res. 2009;89:810-819.
  2. Yucel YH, Cardinell K, Khattak S, et al. Active Lymphatic Drainage From the Eye Measured by Noninvasive Photoacoustic Imaging of Near-Infrared Nanoparticles. Invest Ophthalmol Vis Sci. 2018;59:2699-2707.
  3. Toris CB, Yablonski ME, Wang YL, Camras CB. Aqueous humor dynamics in the aging human eye. Am J Ophthalmol. 1999;127:407-412.
  4. Akiyama G, Saraswathy S, Bogarin T, et al. Functional, structural, and molecular identification of lymphatic outflow from subconjunctival blebs. Exp Eye Res. 2020;196:108049.
  5. Park DY, Lee J, Park I, et al. Lymphatic regulator PROX1 determines Schlemm's canal integrity and identity. J Clin Invest. 2014;124:3960-3974.

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