RESUMEN
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.
Asunto(s)
Ojo/ultraestructura , Vasos Linfáticos/ultraestructura , Microscopía Confocal/métodos , Puntos Cuánticos , Imagen de Cuerpo Entero/métodos , Animales , Técnica del Anticuerpo Fluorescente , Ganglios Linfáticos/ultraestructura , Masculino , RatonesRESUMEN
PURPOSE: Ocular lymphatics have been recently shown to contribute to aqueous humor outflow. It is not yet known whether lymphatic outflow can be stimulated by pharmacological agents. Here we determine whether latanoprost, a prostaglandin F2 alpha analog commonly used to lower IOP to treat glaucoma, increases lymphatic drainage from the eye. METHODS: Lymphatic drainage in mice was assessed in vivo, in 11 latanoprost-treated and 11 control animals using hyperspectral imaging at multiple times following quantum dot (QD) injection into the eye. QD signal intensity was also measured in tissue sections using hyperspectral imaging. RESULTS: In the latanoprost-treated group, lymphatic drainage rate into the submandibular lymph node was increased compared with controls (1.23 ± 1.06 hours-1 vs. 0.30 ± 0.17 hours-1, mean ± SD, P < 0.02). Total QD signal intensity in the submandibular lymph node was greater in the latanoprost-treated group compared with controls (10.55 ± 1.12 vs. 9.48 ± 1.24, log scale, P < 0.05). CONCLUSIONS: This is the first evidence that latanoprost increases lymphatic drainage from the eye. The pharmacological manipulation of this newly identified lymphatic outflow pathway may be relevant to treatments aimed at lowering intraocular pressure in glaucoma. TRANSLATIONAL RELEVANCE: This is the first evidence that a prostaglandin drug widely prescribed for glaucoma, enhances lymphatic drainage from the eye. The pharmacological stimulation of this newly identified outflow pathway may be highly relevant to treatments aimed at lowering IOP to prevent blindness from glaucoma.