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Editors Selection IGR 15-3

Basic Science: Prostaglandins and lymphatic drainage

Comment by Elke Lütjen-Drecoll on:

54743 Latanoprost Stimulates Ocular Lymphatic Drainage: An In Vivo Nanotracer Study, Tam AL; Gupta N; Zhang Z et al., Translational vision science & technology, 2013; 2: 3

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In-vivo experimental studies investigating mechanisms underlying the effects of glaucoma therapy have increasingly been performed in mouse eyes, because in contrast to many other mammals - but similar to primates - mice have a well-developed Schlemm's canal, a lamellated trabecular meshwork ™ and a ciliary muscle that through its tendinous insertion into the TM participates in regulation of outflow resistance. Measurements of IOP and conventional outflow facility in response to outflow drugs show similar results in mice as in primates.

The group of Tam et al. Used an interesting approach to study the effect of latanoprost on uveoscleral outflow in mouse eyes. They used hyperspectral imaging at multiple times following quantum dot injection into the left eye of latanoprost-treated animals and measured the signal of the tracer not only within the eye, but also in the submandibular lymph nodes, known to be the regional lymph nodes for lymphatic drainage from the orbit. They found that treatment with latanoprost leads to an increase in tracer accumulation in the submandibular lymph nodes of treated animals, compared to an untreated control group. The fact that the tracer was also seen in the control group, but at a later time point, suggests that also in untreated mice a fraction of outflow of the tracer normally leaves the eye via unconventional, uveoscleral outflow that is increased by latanoprost treatment.

These studies are especially interesting in mice because morphological demonstration of widening of the uveoscleral pathways in latanoprost treated animals, as shown in primates, is very difficult to demonstrate in mice, on account of the big lens that tends to alter the size of aqueous spaces while cutting sections. There have been attempts to study the effect of latanoprost on uveoscleral outflow in mice using direct or indirect measurements,^1,2 but these authors found only an increase in conventional outflow. Therefore, this study is among the first to demonstrate that the mouse reacts by increasing uveoscleral outflow in response to latanoprost similar to primates, and mice are therefore useful for further studies of unconventional outflow.

The presence of tracers within the submandibular lymph node does not provide convincing support that latanoprost acts directly on lymphatics within the eye

However, it is well-known that uveoscleral outflow ‐ independent of whether the interstitial fluid spaces are uveoscleral routes or true lymphatic vessels within the eye ‐ will deliver tracers into the orbit. From the orbit, fluid and tracers will be collected by lymphatic vessels outside of the eye and will drain into the submandibular lymph nodes that serve as the regional lymph nodes of the orbit. There are studies by the late Wayne Streilein documenting this route of lymphatic drainage. Therefore, if uveoscleral outflow is increased, regardless of the presence of true lymphatic vessels in the eye or not, tracers will enter the orbit and will drain to the submandibular lymph nodes. The presence of tracers within the submandibular lymph node does not provide convincing support that latanoprost acts directly on lymphatics within the eye.

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