Contribution of lymphatic drainage system in corneal allograft rejection in mice

Hoffmann, Friedrich; Zhang, Er-Ping; Mueller, A R; Schulte, Felix; Foss, Hans‐Dieter; Franke, Juergen; Coupland, Sarah E.

doi:10.1007/s00417-001-0384-4

Cited by 32 publications

(26 citation statements)

References 21 publications

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“…The production of IFN-␥ by T cells in these same SMLNs was also induced following allogeneic corneal transplantation implicating SMLN in corneal rejection (66). However, in a separate study, corneal graft survival was greatly enhanced by the excision of superficial CLN and FLN but not SMLN (67,68).…”

Section: Discussionmentioning

confidence: 88%

“…The presence of Ag ϩ cells in the subcapsular sinus of the draining LNs (SMLN, FLN, and CLN), in contrast, indicate that at least a portion of the Ag placed in the AC somehow gains access to lymph vessels in the head and neck. Although it is generally accepted that the internal compartments and uveal tract of the eye are devoid of lymphatic drainage, recent evidence suggests that a connection between the eye and local LNs exists (8,10,65,66). Melanoma cells placed in the AC (9) gain access to LNs in the neck suggesting that a similar connection exists for nonsoluble cell-associated Ags.…”

Section: Discussionmentioning

confidence: 99%

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The Distribution of Antigen in Lymphoid Tissues following Its Injection into the Anterior Chamber of the Rat Eye

Camelo

Shanley

Voon

et al. 2004

The Journal of Immunology

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Injection of Ag into the anterior chamber (AC) of the eye induces deviant immune responses. It has been proposed that Ag internalized by ocular APCs is presented in a tolerogenic fashion in the spleen. However, the nature and distribution of the Ag-bearing cells in the lymphoid organs remain unclear. Fluorescent-labeled Ag (dextran, BSA) injected into the AC of Lewis rats was detected in the subcapsular sinus of the right submandibular lymph nodes (LNs) and cervical LNs, the marginal zone of the spleen, and the medulla of the mesenteric LNs. In the spleen, Ag-bearing cells were CD1+, CD11b+, ED1+, ED2low, ED3+, CD86low, OX6+, CD11c−, ED5− and in the LNs were CD4+, CD8+, CD80+, and OX41+ suggesting these were lymphoid organ resident macrophages. These Ag-bearing macrophages were located adjacent to CD4+ cells, CD8+ cells, and NK cells in the LNs and spleen and to marginal zone B cells in the spleen. No interaction with γδ T cells was observed. The data demonstrates that Ag derived from the AC of the eye is mainly internalized by resident macrophages in the LNs and spleen which are ideally placed to interact with cells involved in the induction of deviant ocular immune responses. The extensive distribution of Ag in LNs draining the upper airway and gastrointestinal tracts, together with the phenotype of Ag-bearing cells in the lymphoid organs, suggests that Ag leaves the eye predominantly in a soluble form and implies other mechanisms of tolerance may contribute to ocular-specific immune responses.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

The Distribution of Antigen in Lymphoid Tissues following Its Injection into the Anterior Chamber of the Rat Eye

Camelo

Shanley

Voon

et al. 2004

The Journal of Immunology

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“…It has been shown in a few studies that antigen presenting cells that have been derived from the eye can be directly drained to the spleen via blood (Wilbanks and Streilein,1990Wilbanks et al, 1991). Despite this belief that antigens of the anterior humor can directly drain into the blood without any anatomical lymphatic drainage, it has been demonstrated that soluble antigens reach the lymph nodes in the neck after injections into the anterior chamber (Hoffman et al, 2001;Boonman et al, 2004;Camelo et al, 2006;Yücel et al, 2009). This suggests that the lack of an effective immune response to intraocular antigens is not due to an inability to recognize intraocular antigens, but rather a lack of an effective immune response to develop and persist after antigen recognition or peripheral tolerance.…”

Section: Immunological Perspectivementioning

confidence: 99%

A model to measure lymphatic drainage from the eye

Kim

Johnston

Gupta

et al. 2011

Experimental Eye Research

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Intraocular pressure (IOP) is the most important risk factor for glaucoma development and progression. Most anti-glaucoma treatments aim to lower IOP by enhancing aqueous humor drainage from the eye. Aqueous humor drainage occurs via well-characterized trabecular meshwork (TM) and uveoscleral (UVS) pathways, and the recently described ciliary lymphatics.The relative contribution of the lymphatic pathway to aqueous drainage is not known. We developed a sheep model to quantitatively assess lymphatic drainage along with TM and UVS outflows. Following intracameral injection of 125 I-bovine serum albumin (BSA), lymph and blood samples were continuously collected. Lymphatic and TM drainage were quantitatively assessed by measuring 125 I-BSA recovery. This quantitative sheep model enables assessment of relative contributions of lymphatic drainage (1.64% ± 0.89%), TM (68.86% ± 9.27%) and UVS outflows (19.87% ± 5.59%), and may help to better understand the effects of glaucoma agents on outflow pathways.iii DedicationThis thesis is dedicated to my parents and little brother for their love, endless support and encouragement.iv

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“…An alternative route through interstitial spaces, the uveoscleral outflow, enables part of the aqueous humor (ϳ16%) (39) to escape into the extraorbital conjunctival tissues (40,41). This route of drainage was first identified in studies from the 1960s of human and monkey eyes (40,41), but the exact path or paths of the outflow have not been well defined.…”

Section: Routes Of Ag Out Of the Eyementioning

confidence: 99%

APCs in the Anterior Uveal Tract Do Not Migrate to Draining Lymph Nodes

Dullforce

Garman²,

Seitz³

et al. 2004

The Journal of Immunology

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The migration of APCs from sites of infection and their maturation are critical elements in the generation of immune responses. However, the paths by which intraocular Ags migrate to draining lymph nodes are not known because the eye has limited lymphatic vessels. To date, only dendritic cells from the cornea and conjunctiva have been shown to emigrate. We demonstrate that phagocytic APCs in the anterior uveal tissues of the murine eye that ingest fluorescent latex beads do not migrate to regional lymph nodes. The beads are ingested in the uveal tract by cells expressing MHC class II, CD11c, or F4/80. Using intravital time-lapse videomicroscopy to monitor iris APC migration after anterior chamber injection of fluorescent Ag, fluorescently labeled APCs fail to move at multiple observation times, even in the presence of Ag and LPS. Whereas an as yet unidentified ocular nonphagocytic APC subset might migrate from the anterior uveal tissues, it is more probable that immune responses in the draining lymph nodes are engendered by soluble Ag escaping the eye through interstitial spaces. The inability of anterior uveal tissue APCs to migrate to lymph nodes may contribute to deviant immune responses that dominate after Ags are introduced into the anterior chamber.

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Contribution of lymphatic drainage system in corneal allograft rejection in mice

Abstract: Our data confirm the existence of functional lymphatic drainage via the uveoscleral pathway and conjunctiva in the mouse. Cells within the ipsilateral submandibular lymph node respond to stimuli upstream. This reaction could potentially be manipulated to improve graft survival.

Cited by 32 publications

References 21 publications

The Distribution of Antigen in Lymphoid Tissues following Its Injection into the Anterior Chamber of the Rat Eye

The Distribution of Antigen in Lymphoid Tissues following Its Injection into the Anterior Chamber of the Rat Eye

A model to measure lymphatic drainage from the eye

APCs in the Anterior Uveal Tract Do Not Migrate to Draining Lymph Nodes

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