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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 7

Pathological ocular lymphangiogenesis.

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Pathological ocular lymphangiogenesis.
(A–C) Short lymphatic sprouts are...
(A–C) Short lymphatic sprouts are found in the nasal-side limbal lymphatics. Lateral views of the nasal side (A) and temporal side (B) of a healthy Prox1-tdTomato mouse eye (8 weeks) demonstrate the predominant presence of limbal lymphatic sprouts in the nasal side. A part of the nasal and temporal lymphatics was enlarged and shown in the insets. Black arrows, sprouts from the limbal lymphatic vessel; black arrowhead, the limbal lymphatic vessel; S, Schlemm’s canal; me, medial rectus muscle. (C) The number of limbal lymphatic sprouts in the nasal versus temporal quadrant was quantified (n = 6, both sexes). (D–F) Extensive corneal lymphangiogenesis in the postnatal Prox1-EGFP rat eye (P7) due to unknown causes. White arrows point to Schlemm’s canal, and a bracket marks active corneal lymphangiogenesis. Boxed areas in panel D are enlarged in panels E and F, respectively. (G–I) Concurrent occurrence of developmental (arrowhead-marked) and pathological (arrow-marked) lymphangiogenesis detected in the eye of a Prox1-EGFP neonate mouse (P0.5). Boxed areas in panel G are enlarged in panels H (original magnification, ×2) and I (original magnification, ×2.2), respectively.

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