Quantum dots trace lymphatic drainage from the mouse eye

Abstract

Glaucoma is a leading cause of blindness in the world, often associated with elevated eye pressure. Currently, all glaucoma treatments aim to lower eye pressure by improving fluid exit from the eye. We recently reported the presence of lymphatics in the human eye. The lymphatic circulation is known to drain fluid from organ tissues and, as such, lymphatics may also play a role in draining fluid from the eye. We investigated whether lymphatic drainage from the eye is present in mice by visualizing the trajectory of quantum dots once injected into the eye. Whole-body hyperspectral fluorescence imaging was performed in 17 live mice. In vivo imaging was conducted prior to injection, and 5, 20, 40 and 70 min, and 2, 6 and 24 h after injection. A quantum dot signal was observed in the left neck region at 6 h after tracer injection into the eye. Examination of immunofluorescence-labelled sections using confocal microscopy showed the presence of a quantum dot signal in the left submandibular lymph node. This is the first direct evidence of lymphatic drainage from the mouse eye. The use of quantum dots to image this lymphatic pathway in vivo is a novel tool to stimulate new treatments to reduce eye pressure and prevent blindness from glaucoma.

Active Lymphatic Drainage From the Eye Measured by Noninvasive Photoacoustic Imaging of Near-Infrared Nanoparticles

“…20 The distribution of the trapped quantum dots in the subcapsular sinus close to one pole of the node matches closely the afferent flow into the node. 67 It is reasonable that the smaller tracer CF770/BSA would make its way to the parenchyma.…”

“…18,19 Less invasive mouse studies using quantum dots and hyperspectral imaging of live mice, tracked lymphatic drainage from the anterior chamber to the ipsilateral submandibular node. 20,21 While these experiments were more amenable than studies performed in sheep, limitations included the use of a tracer with potential toxicity 22 and the inability to quantify drainage in vivo. 21 Thus, the development of noninvasive quantitative techniques, with nonradioactive and nontoxic tracers would greatly aid our understanding of lymphatic drainage from the eye in health and disease.…”

Nanotechnology and glaucoma: a review of the potential implications of glaucoma nanomedicine

“…Tam and colleagues used quantum dots, such as CdSe/ZnS core/shell nanoparticles, to trace live images of lymphatic drainage from mouse eyes 36. Quantum dots, unlike conventional methods for observing the lymphatic network, are ideal for non-invasive in vivo imaging due to their broad excitation spectra, narrow and tunable emission spectra and high photobleaching threshold.…”

Author Response: Sufficient Evidence for Lymphatics in the Developing and Adult Human Choroid?

“…As such, a major aim of our study was to use immunohistochemical and ultrastructural approaches to discover the most compelling evidence we could for lymphatic-like structures in the human choroid. Numerous studies to date have struggled to identify a system of ''true lymphatics'' in the anterior and posterior eye, [7][8][9] although there is now functional [10][11][12] and anatomical evidence in support of lymphatic-like systems within the human anterior angle, 13 iris, and ciliary body, 14 and in our own study of the choroid.…”