Lymphatics in Eye Fluid Homeostasis: Minor Contributors or Significant Actors?

Subileau, Mariela; Vittet, Daniel

doi:10.3390/biology10070582

Cited by 11 publications

(5 citation statements)

References 115 publications

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“…The presence of ciliary body lymphatics has also been investigated by several other groups; however, the results were conflicting. One consistent finding of these studies was the presence of LYVE1-positive cells in the ciliary body stroma and processes [ 74 , 75 , 76 , 77 ]. Interestingly, the majority of these cells was also immunoreactive for CD68 (a well-known macrophage marker), indicating that these cells might belong to the macrophage lineage [ 75 ].…”

Section: Lymphatic Systemmentioning

confidence: 67%

“…In common with the brain, both the retina and optic nerve parenchyma lack a lymphatic system [ 67 ], suggesting that they might possess an alternative system for fluid homeostasis and waste clearance. The high metabolic activity of retinal neuron resulting in the generation of neurotoxic waste products also supports the notion that the retina might have an alternative waste-clearance pathway [ 77 ]. Moreover, the retina and optic nerve also have astrocytes and AQP4 water channels on the astrocytic endfeet [ 30 , 130 , 131 ].…”

Section: Glymphatic Systemmentioning

confidence: 70%

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Ocular Lymphatic and Glymphatic Systems: Implications for Retinal Health and Disease

Uddin

Rutar

2022

IJMS

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Clearance of ocular fluid and metabolic waste is a critical function of the eye in health and disease. The eye has distinct fluid outflow pathways in both the anterior and posterior segments. Although the anterior outflow pathway is well characterized, little is known about posterior outflow routes. Recent studies suggest that lymphatic and glymphatic systems play an important role in the clearance of fluid and waste products from the posterior segment of the eye. The lymphatic system is a vascular network that runs parallel to the blood circulatory system. It plays an essential role in maintenance of fluid homeostasis and immune surveillance in the body. Recent studies have reported lymphatics in the cornea (under pathological conditions), ciliary body, choroid, and optic nerve meninges. The evidence of lymphatics in optic nerve meninges is, however, limited. An alternative lymphatic system termed the glymphatic system was recently discovered in the rodent eye and brain. This system is a glial cell-based perivascular network responsible for the clearance of interstitial fluid and metabolic waste. In this review, we will discuss our current knowledge of ocular lymphatic and glymphatic systems and their role in retinal degenerative diseases.

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Section: Lymphatic Systemmentioning

confidence: 67%

Section: Glymphatic Systemmentioning

confidence: 70%

Ocular Lymphatic and Glymphatic Systems: Implications for Retinal Health and Disease

Uddin

Rutar

2022

IJMS

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“…One mechanism by which fibroblasts may transdifferentiate into myofibroblasts is via exposure to POAG-related extracellular signal molecules such as TGF-β2 which is upregulated in the aqueous humour (AH) of POAG patients [ 8 , 40 ]. It is plausible that AH containing POAG-associated ROS and cytokines can reach Tenon’s capsule and therefore TFs by drainage via the subconjunctival space and/or lymphatic vessels of the conjunctiva [ 41 ]. Also, TGF-β1 can cause fibroblast to myofibroblast transdifferentiation [ 42 , 43 ] and may play an autocrine role in our experiment via a positive feedback mechanism because TGF-β1 (TGFB1) was upregulated in glaucomatous TF cells when compared to normal cells in our results.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide RNA sequencing of ocular fibroblasts from glaucomatous and normal eyes: Implications for glaucoma management

Roodnat,

Callaghan,

Doyle

et al. 2024

PLoS ONE

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Primary open angle glaucoma is a leading cause of visual impairment and blindness which is commonly treated with drugs or laser but may require surgery. Tenon’s ocular fibroblasts are involved in wound-healing after glaucoma filtration surgery and may compromise a favourable outcome of glaucoma surgery by contributing to fibrosis. To investigate changes in gene expression and key pathways contributing to the glaucomatous state we performed genome-wide RNA sequencing. Human Tenon’s ocular fibroblasts were cultured from normal and glaucomatous human donors undergoing eye surgery (n = 12). mRNA was extracted and RNA-Seq performed on the Illumina platform. Differentially expressed genes were identified using a bioinformatics pipeline consisting of FastQC, STAR, FeatureCounts and edgeR. Changes in biological functions and pathways were determined using Enrichr and clustered using Cytoscape. A total of 5817 genes were differentially expressed between Tenon’s ocular fibroblasts from normal versus glaucomatous eyes. Enrichment analysis showed 787 significantly different biological functions and pathways which were clustered into 176 clusters. Tenon’s ocular fibroblasts from glaucomatous eyes showed signs of fibrosis with fibroblast to myofibroblast transdifferentiation and associated changes in mitochondrial fission, remodeling of the extracellular matrix, proliferation, unfolded protein response, inflammation and apoptosis which may relate to the pathogenesis of glaucoma or the detrimental effects of topical glaucoma therapies. Altered gene expression in glaucomatous Tenon’s ocular fibroblasts may contribute to an unfavourable outcome of glaucoma filtration surgery. This work presents a genome-wide transcriptome of glaucomatous versus normal Tenon’s ocular fibroblasts which may identify genes or pathways of therapeutic value to improve surgical outcomes.

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“…From blebs, AH filters through conjunctival vessels and lymphatics [ 6 , 7 , 28 , 29 , 30 , 31 , 32 ]. Benedikt O.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Optical Coherence Tomography Evidence of Aqueous Humor Flow from the Suprachoroidal Space to Conjunctival Lymphatics

Kumar,

Bezzabotnov,

Rustamova

et al. 2023

Vision

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A surgical technique was developed to enhance aqueous humor (AH) flow through the non-trabecular outflow pathway by rerouting it from the anterior chamber (AC) to the suprachoroidal space (SCS) without detaching the ciliary body from the scleral spur. Medium- and long-term surgical outcomes were retrospectively analyzed in a case series of 58 glaucoma patients. At 6, 12, and 24 months, the mean IOP decreased from 27.8 ± 8.3 to 14.9 ± 5.0 mmHg, median 15.0 (25th percentile (p25)13.0; 75th percentile (p75) 18.0) and 15.2 ± 3.3 mmHg, and hypotensive medication use reduced from a median (p25; p75) of 3 (2; 3) to 0 (0; 2), 0 (0; 2), and 0 (0; 1.5), respectively. Intra- and postoperative complications were few and manageable. Following surgery, no bleb formation occurred in any of the cases (as confirmed by optical coherence tomography). Conjunctival lymphatic vessels (CLVs) developed in 50% of eyes (29/58). Clinically, they developed directly from sclera and had no connection to the surgical site. Analysis further showed that the development of CLVs and their longer visibility period had poor prognostic value for IOP control. If the fluid flow from the SCS to CLVs was resistance-free, no CLV development was evident. However, if any resistance existed in the flow, the fluid accumulated in lymphatics, resulting in their engorgement. The proposed technique was safe and effective in decreasing IOP in glaucoma patients by enhancing AH flow from the SCS to CLVs via connecting intrascleral microchannels.

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Lymphatics in Eye Fluid Homeostasis: Minor Contributors or Significant Actors?

Cited by 11 publications

References 115 publications

Ocular Lymphatic and Glymphatic Systems: Implications for Retinal Health and Disease

Ocular Lymphatic and Glymphatic Systems: Implications for Retinal Health and Disease

Genome-wide RNA sequencing of ocular fibroblasts from glaucomatous and normal eyes: Implications for glaucoma management

Clinical and Optical Coherence Tomography Evidence of Aqueous Humor Flow from the Suprachoroidal Space to Conjunctival Lymphatics

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