Identification of lymphatics in the ciliary body of the human eye: A novel “uveolymphatic” outflow pathway

Yücel, Yeni H.; Johnston, Mary; Ly, Tina; Patel, Manoj; Drake, Brian; Gümüş, Ersin; Fraenkl, Stephan A.; Moore, Sara; Tobbia, Dalia; Armstrong, David W.; Horváth, Éva; Gupta, Neeru

doi:10.1016/j.exer.2009.08.010

Cited by 155 publications

(133 citation statements)

References 37 publications

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“…27 Given the notion that the globe is devoid of lymphatic vessels 30 and a mature population of lymphocytes, 45 it seems that intraocular lymphoma should be considered stage 5 disease. However, results of recent studies 32,33 suggest that lymphatic vessels exist in the anterior aspect of the uvea of clinically normal sheep and humans. Thus, although the absence of a mature population of lymphocytes in eyes precludes its classification as a secondary lymphoid organ, the presence of lymphatic vessels may indicate eyes are a tertiary lymphoid organ; this would indicate intraocular lymphoma should be classified as stage 1 disease for species with uveal lymphatic vessels.…”

Section: Discussionmentioning

confidence: 99%

“…30 Thus, intraocular lymphomas likely should be classified as stage 5 tumors on the basis of World Health Organization guidelines. However, results of recent studies of sheep 31 and humans 32,33 indicate uveal tissue may have lymphatic channels, suggesting that a revision of this classification scheme may be necessary to improve determination of a prognosis for patients with lymphoma at only an ocular site. To the authors' knowledge, only reports of single cats or dogs with PSOL have been published.…”

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confidence: 99%

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Presumed solitary intraocular or conjunctival lymphoma in dogs and cats: 9 cases (1985–2013)

Wiggans¹,

Skorupski²,

Reilly³

et al. 2014

javma

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Objective—To determine prevalence, reason for evaluation, treatment, and outcome for dogs and cats with presumed solitary ocular lymphoma (PSOL). Design—Retrospective case series. Animals—7 dogs and 2 cats with PSOL. Procedures—Medical records were reviewed. Progression-free survival time (PFST) and overall survival time (OST) were determined. Results—Animals with intraocular (4 dogs and 1 cat) or conjunctival (3 dogs and 1 cat) lymphoma represented 0.1% and 0.08% of patients with lymphoma evaluated at the hospital during the study period, respectively. Animals with intraocular lymphoma represented 0.19% of all patients with uveitis; animals with conjunctival lymphoma represented 0.16% of all patients with conjunctivitis. Tumors included B-cell (2 intraocular and 1 conjunctival), non–B-cell, non–T-cell (1 intraocular), and T-cell (3 conjunctival) neoplasms; immunophenotype of 2 uveal lymphomas was not determined. Treatments included enucleation (4 intraocular) and chemotherapy (3 intraocular and 2 conjunctival). All dogs with intraocular lymphoma developed neurologic signs. Lymph node metastasis was detected in 2 patients with conjunctival lymphoma. Median PFST and OST were 178 days for all animals with PSOL, dogs with PSOL, and animals with intraocular lymphoma. Median PFST and OST for animals with conjunctival lymphoma were 221 and 549 days, respectively. Conclusions and Clinical Relevance—Results indicated PSOL was uncommon, but should be considered a differential diagnosis for animals with uveitis or conjunctivitis. Performance of MRI and cytologic analysis of CSF and regional lymph node aspirate samples may be beneficial for such patients. Prognosis seemed to be better for animals with conjunctival lymphoma than it was for those with intraocular lymphoma.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Presumed solitary intraocular or conjunctival lymphoma in dogs and cats: 9 cases (1985–2013)

Wiggans¹,

Skorupski²,

Reilly³

et al. 2014

javma

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“…The histogram shows radioactivity counts in regional lymph nodes compared to the reference popliteal site, 4 hours post intracameral tracer injection. There were significant differences in radioactivity counts in submandibular, retropharyngeal, preauricular and cervical nodes compared to popliteal site by one-way repeated ANOVA measures followed by single degree of freedom contrasts for each site (P < 0.05) (Yücel et al, 2009) …”

Section: Evidence For the Presence Of Lymphatic Channels In The Eyementioning

confidence: 94%

“…Yücel and colleagues were able to detect lymphatic vessels in the ciliary body using D2-40 ( Figure 2) in humans, and in the sheep ciliary body, the results were confirmed with LYVE-1 markers. This strongly suggests that lymphatics are present in the eye (Yücel et al, 2009). …”

Section: Evidence For the Presence Of Lymphatic Channels In The Eyementioning

confidence: 96%

“…Additionally, fluorescent nanospheres were injected into the anterior chamber of sheep and were found to localize in the lumen of LYVE-1 positive lymphatic channels in the ciliary body. This suggests the roles of these channels in transporting particles from the anterior chamber (Yücel et al, 2009). The histogram shows radioactivity counts in regional lymph nodes compared to the reference popliteal site, 4 hours post intracameral tracer injection.…”

Section: Evidence For the Presence Of Lymphatic Channels In The Eyementioning

confidence: 97%

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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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Intraocular Lymphatics in Ciliary Body Melanomas With Extraocular Extension

Heindl

Hofmann²,

Schrödl³

et al. 2010

Arch Ophthalmol

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To assess the functional significance of intraocular tumor-associated lymphatic vessels in ciliary body melanomas with extraocular extension. Methods: Twelve consecutive patients enucleated for a malignant melanoma of the ciliary body with extraocular extension and immunohistochemical presence of intraocular LYVE-1-positive and podoplanin-positive lymphatic vessels were examined for proliferation status and tumor invasion into tumor-associated lymphatics. Proliferating lymphatic vessels were identified using LYVE-1 and podoplanin as specific lymphatic endothelial markers and Ki-67 as the proliferation marker. Tumor invasion into lymphatic vessels was assessed using Melan-A as the melanoma marker. Kaplan-Meier analyses of survival and metastasis were performed. Results: Intraocular proliferating lymphatic vessels were detected in all 12 ciliary body melanomas with extra

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Identification of lymphatics in the ciliary body of the human eye: A novel “uveolymphatic” outflow pathway

Cited by 155 publications

References 37 publications

Presumed solitary intraocular or conjunctival lymphoma in dogs and cats: 9 cases (1985–2013)

Presumed solitary intraocular or conjunctival lymphoma in dogs and cats: 9 cases (1985–2013)

A model to measure lymphatic drainage from the eye

Intraocular Lymphatics in Ciliary Body Melanomas With Extraocular Extension

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