Lymphatic vessels of the eye – old questions – new insights

Grüntzig, J; Hollmann, Frank

doi:10.1016/j.aanat.2018.08.004

Cited by 28 publications

(20 citation statements)

References 72 publications

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“…Using LSFM, we bring novel insights in the visualization of the whole topography of the ocular surface lymphatic networks. Our results are in accordance with the known existence of a dense network of superficial lymphatics in the corneolimbus and the conjunctiva 7 , 11 . Moreover, we showed in this study that this network has a characteristic spatially organized distribution around the eyeball, with large collecting trunks draining at the inner nasal canthus.…”

Section: Discussionsupporting

confidence: 92%

“…Lymphatic vessels are present in the eye corneolimbus and in the superficial eye conjunctiva 7 , 8 . Some studies have also postulated for the existence of lymphatics in more internal parts of the eye such as the ciliary body and/or the choroid, but these statements remain controversial and need to be further confirmed 9 – 11 . Lymphatics of the anterior segment of the eye appeared to be potentially involved in the drainage of aqueous humor.…”

Section: Introductionmentioning

confidence: 99%

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Eye lymphatic defects induced by bone morphogenetic protein 9 deficiency have no functional consequences on intraocular pressure

Subileau

Acar

Carret

et al. 2020

Sci Rep

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Aqueous humor drainage is essential for the regulation of intraocular pressure (IOP), a major risk factor for glaucoma. The Schlemm’s canal and the non-conventional uveoscleral pathway are known to drain aqueous humor from the eye anterior chamber. It has recently been reported that lymphatic vessels are involved in this process, and that the Schlemm’s canal responds to some lymphatic regulators. We have previously shown a critical role for bone morphogenetic protein 9 (BMP9) in lymphatic vessel maturation and valve formation, with repercussions in drainage efficiency. Here, we imaged eye lymphatic vessels and analyzed the consequences of Bmp9 (Gdf2) gene invalidation. A network of lymphatic vessel hyaluronan receptor 1 (LYVE-1)-positive lymphatic vessels was observed in the corneolimbus and the conjunctiva. In contrast, LYVE-1-positive cells present in the ciliary bodies were belonging to the macrophage lineage. Although enlarged conjunctival lymphatic trunks and a reduced valve number were observed in Bmp9-KO mice, there were no morphological differences in the Schlemm’s canal compared to wild type animals. Moreover, there were no functional consequences on IOP in both basal control conditions and after laser-induced ocular hypertonia. Thus, the BMP9-activated signaling pathway does not constitute a wise target for new glaucoma therapeutic strategies.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Eye lymphatic defects induced by bone morphogenetic protein 9 deficiency have no functional consequences on intraocular pressure

Subileau

Acar

Carret

et al. 2020

Sci Rep

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“…Advantages of applying gene therapy to treat IRDs reside in (1) the accessibility of imaging and surgery with innovative and non-invasive techniques; (2) the tiny size of the retina, which requires small amounts of therapeutics to be administered; (3) the ocular immune privilege, due to the presence of the blood–retinal barrier [4], and the lack of lymphatic vessels, although the issue is still controversial [5], all of which make the eye a compartmentalized reservoir with privileged immunological defenses for good tolerance of gene therapy [6]; (4) the possibility of treating one eye and considering the untreated eye as an ideal control for the efficacy and safety of the treatment, with IRDs being bilateral; and, finally, (5) the availability of a wide range of animal models to test experimental therapies [7]. A main disadvantage is the post-mitotic nature of retinal tissues.…”

Section: Introductionmentioning

confidence: 99%

Gene Therapy in Retinal Dystrophies

Ziccardi

Cordeddu

Gaddini

et al. 2019

IJMS

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Inherited retinal dystrophies (IRDs) are a group of clinically and genetically heterogeneous degenerative disorders. To date, mutations have been associated with IRDs in over 270 disease genes, but molecular diagnosis still remains elusive in about a third of cases. The methodologic developments in genome sequencing techniques that we have witnessed in this last decade have represented a turning point not only in diagnosis and prognosis but, above all, in the identification of new therapeutic perspectives. The discovery of new disease genes and pathogenetic mechanisms underlying IRDs has laid the groundwork for gene therapy approaches. Several clinical trials are ongoing, and the recent approval of Luxturna, the first gene therapy product for Leber congenital amaurosis, marks the beginning of a new era. Due to its anatomical and functional characteristics, the retina is the organ of choice for gene therapy, although there are quite a few difficulties in the translational approaches from preclinical models to humans. In the first part of this review, an overview of the current knowledge on methodological issues and future perspectives of gene therapy applied to IRDs is discussed; in the second part, the state of the art of clinical trials on the gene therapy approach in IRDs is illustrated.

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“…Dye injections demonstrated that the pericorneal lymphatic ring opens into conjunctival lymphatic lacunae (lakes) which, in turn, form superficial and deep networks 24 . In a different study, these lacunae were indicated as ‘lymphatic bulbs’ 19 …”

Section: Discussionmentioning

confidence: 99%

Lymphatic lacunae of the human eye conjunctiva embedded within a stroma containing CD34⁺ telocytes

Nicolescu

Rusu

Voinea

et al. 2020

J Cellular Molecular Medi

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An accurate identification of telocytes (TCs) was limited because of the heterogeneity of cell types expressing the markers attributed to TCs. Some endothelial lineage cells also could fit within the pattern of TCs. Such endothelial cells could line conjunctival lacunae previously assessed by laser confocal microscopy. We have been suggested that an accurate distinction of TCs from endothelial cells in the human eye conjunctiva could be achieved by use of CD31, CD34 and D2‐40 (podoplanin); and that the conjunctival lacunae are in fact lymphatic. We aimed as testing the hypothesis by an immunohistochemical study on human eye conjunctiva biopsy samples. Samples of human eye conjunctiva from 30 patients were evaluated immunohistochemically by use of the primary antibodies: CD34, D2‐40 and CD31. D2‐40 was equally expressed within epithelia and laminae propria. Basal epithelial cells were D2‐40 positive. Within the stromal compartment, the lymphatic marker D2‐40 labelled several lymphatic vessels. CD31 labelled both vascular and lymphatic endothelial cells within the lamina propria. When capillary lymphatics were tangentially cut, they gave the false appearance of telocytes. Blood endothelial cells expressed CD34, whereas lymphatic endothelial cells did not. Stromal CD34‐expressing cells/telocytes were found building a consistent pan‐stromal network which was equally CD31‐negative and D2‐40‐negative. The conjunctival lymphatic lacunae seem to represent a peculiar anatomic feature of eye conjunctiva. They are embedded within a CD34‐expressing stromal network of TCs. The negative expression of CD31 and D2‐40 should be tested when discriminating CD34‐expressing TCs.

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Lymphatic vessels of the eye – old questions – new insights

Cited by 28 publications

References 72 publications

Eye lymphatic defects induced by bone morphogenetic protein 9 deficiency have no functional consequences on intraocular pressure

Eye lymphatic defects induced by bone morphogenetic protein 9 deficiency have no functional consequences on intraocular pressure

Gene Therapy in Retinal Dystrophies

Lymphatic lacunae of the human eye conjunctiva embedded within a stroma containing CD34⁺ telocytes

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Lymphatic vessels of the eye – old questions – new insights

Cited by 28 publications

References 72 publications

Eye lymphatic defects induced by bone morphogenetic protein 9 deficiency have no functional consequences on intraocular pressure

Eye lymphatic defects induced by bone morphogenetic protein 9 deficiency have no functional consequences on intraocular pressure

Gene Therapy in Retinal Dystrophies

Lymphatic lacunae of the human eye conjunctiva embedded within a stroma containing CD34+ telocytes

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Lymphatic lacunae of the human eye conjunctiva embedded within a stroma containing CD34⁺ telocytes