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Organogenesis and distribution of the ocular lymphatic vessels in the anterior eye
Yifan Wu, Young Jin Seong, Kin Li, Dongwon Choi, Eunkyung Park, George H. Daghlian, Eunson Jung, Khoa Bui, Luping Zhao, Shrimika Madhavan, Saren Daghlian, Patill Daghlian, Desmond Chin, Il-Taeg Cho, Alex K. Wong, Martin Heur, Sandy Zhang-Nunes, James C. Tan, Masatsugu Ema, Tina T. Wong, Alex S. Huang, Young-Kwon Hong
Yifan Wu, Young Jin Seong, Kin Li, Dongwon Choi, Eunkyung Park, George H. Daghlian, Eunson Jung, Khoa Bui, Luping Zhao, Shrimika Madhavan, Saren Daghlian, Patill Daghlian, Desmond Chin, Il-Taeg Cho, Alex K. Wong, Martin Heur, Sandy Zhang-Nunes, James C. Tan, Masatsugu Ema, Tina T. Wong, Alex S. Huang, Young-Kwon Hong
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Research Article Development Ophthalmology

Organogenesis and distribution of the ocular lymphatic vessels in the anterior eye

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Abstract

Glaucoma surgeries, such as trabeculectomy, are performed to lower intraocular pressure to reduce risk of vision loss. These surgeries create a new passage in the eye that reroutes the aqueous humor outflow to the subconjunctival space, where the fluid is presumably absorbed by the conjunctival lymphatics. Here, we characterized the development and function of the ocular lymphatics using transgenic lymphatic reporter mice and rats. We found that the limbal and conjunctival lymphatic networks are progressively formed from a primary lymphatic vessel that grows from the nasal-side medial canthus region at birth. This primary lymphatic vessel immediately branches out, invades the limbus and conjunctiva, and bidirectionally encircles the cornea. As a result, the distribution of the ocular lymphatics is significantly polarized toward the nasal side, and the limbal lymphatics are directly connected to the conjunctival lymphatics. New lymphatic sprouts are produced mainly from the nasal-side limbal lymphatics, posing the nasal side of the eye as more responsive to fluid drainage and inflammatory stimuli. Consistent with this polarized distribution of the ocular lymphatics, a higher drainage efficiency was observed in the nasal side than the temporal side of the eye when injected with a fluorescent tracer. In contrast, blood vessels are evenly distributed at the anterior surface of the eyes. Also, we found that these distinct vascular distribution patterns were conserved in human eyes. Together, our study demonstrated that the ocular surface lymphatics are more densely present in the nasal side and uncovered the potential clinical benefits in selecting the nasal side as a glaucoma surgery site to improve fluid drainage.

Authors

Yifan Wu, Young Jin Seong, Kin Li, Dongwon Choi, Eunkyung Park, George H. Daghlian, Eunson Jung, Khoa Bui, Luping Zhao, Shrimika Madhavan, Saren Daghlian, Patill Daghlian, Desmond Chin, Il-Taeg Cho, Alex K. Wong, Martin Heur, Sandy Zhang-Nunes, James C. Tan, Masatsugu Ema, Tina T. Wong, Alex S. Huang, Young-Kwon Hong

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Figure 3

In situ visualization of the lymphatic vessels in the ocular and surrounding tissues.

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In situ visualization of the lymphatic vessels in the ocular and surroun...
(A–F) The whole head of a Prox1-EGFP rat was fixed and partially dissected to reveal the ocular lymphatics surrounding the ocular tissue. (A) Diagram of the rat head showing the region of interest. Bright-field (B) and fluorescence (C) images of the partially skinned head of a Prox1-EGFP rat. (D) Inverted and gray scale image of the ocular lymphatics with 2 boxed areas that are enlarged in panels E and F. The limbal lymphatics (white arrowheads) are directly attached to the conjunctival lymphatics through multiple short branches (white arrows). (G–J) Dense lymphatic networks in the conjunctiva. (G) Simplified diagram showing the superior (H and I) and inferior (J) conjunctiva in the nasal side. (I) The boxed area in panel H was enlarged. Arrow points to the connection between the conjunctival lymphatics and the limbal lymphatics (arrowheads). PC, palpebral conjunctiva; BC, bulbar conjunctiva; Co, cornea. Scale bars: 1 mm. (K–M) The head of a Prox1-tdTomato mouse was fixed and partially skinned to reveal the lymphatics surrounding the ocular tissue. Arrow in panels E and M point to a main lymphatic vessel that exits the ocular tissue and extends toward the medial canthus. Five rats and 7 mice (both sexes) were used for each experiment with comparable results. One representative image is shown for each panel. Original magnification, ×2.7 (D, E, and F), ×3 (I), and ×3.9 (M).

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