LYMPHATIC STRUCTURES OF THE EYE AND UVEOLYMPHATIC (METABOLIC) PATHWAY OF INTRAOCULAR FLUID OUTFLOW. Part 1

PURPOSE: To identify the lymphatic structures of the human eye, study their ultrastructural organization and morphological changes in the ciliary body and the choroid in patients with primary open-angle glaucoma.

METHODS: Fragments of eye tissues enucleated for medical indications (n=28) were studied. The main group included 17 eyes of patients diagnosed with terminal stage primary open-angle glaucoma. The tissues underwent an immunohistochemical study using monoclonal antibodies to markers of the following agents: blood vessel endotheliocytes CD31 and CD34 («Novocasra», Germany), lymphatic endotheliocytes LYVE-1 («Abcam», England), Podoplanin («Monosan», The Netherlands) and Prox-1 («Covance», Germany), fibroblast growth factor receptor marker FGFR («Abcam», England). Obtained eye tissues were studied by means of Leica DME light microscope. Electron microscopy of the eye tissues was carried out using JEM 1400 electron microscope (Japan).

RESULTS: The imunohistochemical and ultrastructural analysis of the ciliary body revealed the presence of lymphatic channels and structured interstitial spaces (tissue slits) formed by collagen fibers and fibroblasts. Lymphatic canals and lacunae were also found in the choroid. Lymphatic channels were located in the vascular capillary layer and were confined to cells similar to fibroblasts and pigment cells, while lymphatic lacunae were found in the suprachoroid layer and were lined with cells similar to fibroblasts. For the first time lymphatic structures were found on the border between the sclera and the lamina cribrosa and in the optic nerve sheath. The ciliary body in patients with terminal primary open-angle glaucoma shows the following structural signs of edema and stromal swelling: interstitial space widening, venous vessels lumen enlargement, reduction of the lymphatic endothelial cells marker expression. Similar processes were found in the choroid during the terminal stage of primary open-angle glaucoma: enlarged blood and lymphatic vessels lumens, pericapillary spaces swelling and enlargement, choriocapillary layer stroma swelling as well as the disruption of the anchoring collagen fibrils binding to myofibroblasts and pigment cells. The study revealed an associated with swelling significant increase in choroid thickness and volume density of the epithelium, interstitial spaces and vessels, which indicated inflammation.

CONCLUSION: The new fundamental data obtained during the study broadens the current understanding of lymphatic system elements presence in the human eye and their changes associated with primary open-angle glaucoma. This allows us to postulate the existence of a lymphatic (uveolymphatic) pathway of intraocular (tissue) fluid outflow, aimed at utilizing and excreting metabolic and cellular destruction products. Structural disturbances of the lymphatic outflow components play an important role in the mechanisms of primary open-angle glaucoma development.

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