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Tailoi Chan-Ling, Mohammad Nasir Uddin, Mark E Koina, Francine F Behar-Cohen, Ping Hu; Compelling structural and functional evidence for glymphatics and lymphatics in human posterior eye: Enhanced immune response and glymphatic/lymphatic changes in glaucoma pathogenesis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4274.
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© ARVO (1962-2015); The Authors (2016-present)
This study aims to provide evidence of lymphatics and glymphatics including their precise location & to detail changes in lymphatics & immune response in glaucoma.
Optic nerve meninges from 30 adult eyes (glaucoma & age matched controls) were examined. Ultrastructural characterization & multi-marker IHC was carried out using D2-40, LYVE-1, VEGFR3 (Lymphatic); UEA Lectin, CD34 (blood vessel); Iba-1 (macrophage); MHC II (antigen presenting cell, APC); GFAP, vimentin (glia), & AQP4 (water channel protein) markers. Indian ink & FITC-dextran were injected into supra-choroidal space of adult Lewis rats to examine lymphatic drainage.
Ultrastructural features of lymphatics including anchoring filaments, luminal flocculent protein but absence of erythrocytes, basal lamina, Weibel-Palade bodies, & fenestrae were shown. Lymphatics were evident in arachnoid mater adjacent to sub-arachnoid space (SAS) in close association with meningothelial cells (MEC). MEC expressed D2-40+ constitutively. IHC showed D2-40+/UEA- collapsed & thin-walled lymphatics in retrolaminar optic nerve meninges. D2-40+/UEA– lymphatics were also found in dura close to D240-/UEA+ blood vessels. Tracer studies in rat showed presence of indian ink filled lymphatic capillary in arachnoid mater showing lymphatic outflow from choriocapillaris to retrolaminar optic nerve. In glaucoma, arachnoid & dural lymphatics had larger lumens indicating lymphatic filling, thicker wall & greater density (78%); increased density (56%) & intensity of D2-40+ expression (69%) of MEC; & increased density of Iba-1+ macrophages (37%), MHC II+ APCs (47%) & Iba-1+/MHC II+ macrophages (75%), p < 0.05 compared to control eyes.
This study has shown in retrolaminar optic nerve, lymphatics are located in both dura & arachnoid mater, where arachnoid lymphatics are spatially related to MEC. This intimate association leads us to suggest that MEC and arachnoid lymphatics form the structural basis for functional interaction between lymphatics and CSF in healthy CNS. The findings also showed increased APCs, macrophages, lymphatic filling & density of MEC in glaucoma. With MEC functions of CSF drainage, pro-inflammatory cytokine expression & waste transport (via AQP4) our findings suggest that lymphatic/MEC interactions are integral to glaucoma pathogenesis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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