Author Response: Sufficient Evidence for Lymphatics in the Developing and Adult Human Choroid?

Chan‐Ling, Tailoi; Koina, Mark; Arfuso, Frank; Adamson, Samuel; Baxter, Laurence A.; Hu, Peng; Madigan, Michele C.

doi:10.1167/iovs.15-18011

Cited by 7 publications

(4 citation statements)

References 22 publications

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“…This view has recently been challenged with reports of vessels that express lymphatic markers within the ciliary body (Yücel et al 2009) and choroid (Koina et al 2015) of human eyes, although these reports have been met with considerable controversy (Schroedl et al 2014; Chan-Ling et al 2015; Heindl et al 2015). If lymphatics are normally present within the eye, then these vessels may contribute to unconventional outflow.…”

Section: Methods Of Measurementmentioning

confidence: 99%

Unconventional aqueous humor outflow: A review

Johnson

McLaren

Overby

2017

Experimental Eye Research

169

120

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Aqueous humor flows out of the eye primarily through the conventional outflow pathway that includes the trabecular meshwork and Schlemm's canal. However, a fraction of aqueous humor passes through an alternative or ‘unconventional’ route that includes the ciliary muscle, supraciliary and suprachoroidal spaces. From there, unconventional outflow may drain through two pathways: a uveoscleral pathway where aqueous drains across the sclera to be resorbed by orbital vessels, and a uveovortex pathway where aqueous humor enters the choroid to drain through the vortex veins. We review the anatomy, physiology and pharmacology of these pathways. We also discuss methods to determine unconventional outflow rate, including direct techniques that use radioactive or fluorescent tracers recovered from tissues in the unconventional pathway and indirect methods that estimate unconventional outflow based on total outflow over a range of pressures. Indirect methods are subject to a number of assumptions and generally give poor agreement with tracer measurements. We review the variety of animal models that have been used to study conventional and unconventional outflow. The mouse appears to be a promising model because it captures several aspects of conventional and unconventional outflow dynamics common to humans, although questions remain regarding the magnitude of unconventional outflow in mice. Finally, we review future directions. There is a clear need to develop improved methods for measuring unconventional outflow in both animals and humans.

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Section: Methods Of Measurementmentioning

confidence: 99%

Unconventional aqueous humor outflow: A review

Johnson

McLaren

Overby

2017

Experimental Eye Research

169

120

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“…In the posterior part of the eye, lymphatic capillaries have been identified in the developing and adult human choroid [ 50 ]. However, in the choroid, especially in the healthy adult human choroid, controversy still remains regarding the presence of classical lymphatics similar to those in the ciliary body [ 79 , 80 , 81 , 82 ]. Although there is to date no report of traditional lymphatic vasculature in the retina and sclera, a large population of non-endothelial LYVE1-positive macrophages was reported in the sclera [ 72 , 83 , 84 , 85 ].…”

Section: Lymphatic Systemmentioning

confidence: 99%

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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“…Together with ischemia, PDR involves edema formation and chronic inflammation, which are both triggers for lymphangiogenesis. As the demand for fluid drainage and immune/inflammatory cell trafficking increases, it is plausible that a lymphatic-like system can emerge during pathological conditions of the posterior eye segment [79,80].…”

Section: Lymphatic Vascular Formation In Ocular Diseasesmentioning

confidence: 99%

Lymphatic Vascular Structures: A New Aspect in Proliferative Diabetic Retinopathy

Gucciardo

Loukovaara

Salvén

et al. 2018

IJMS

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Diabetic retinopathy (DR) is the most common diabetic microvascular complication and major cause of blindness in working-age adults. According to the level of microvascular degeneration and ischemic damage, DR is classified into non-proliferative DR (NPDR), and end-stage, proliferative DR (PDR). Despite advances in the disease etiology and pathogenesis, molecular understanding of end-stage PDR, characterized by ischemia- and inflammation-associated neovascularization and fibrosis, remains incomplete due to the limited availability of ideal clinical samples and experimental research models. Since a great portion of patients do not benefit from current treatments, improved therapies are essential. DR is known to be a complex and multifactorial disease featuring the interplay of microvascular, neurodegenerative, metabolic, genetic/epigenetic, immunological, and inflammation-related factors. Particularly, deeper knowledge on the mechanisms and pathophysiology of most advanced PDR is critical. Lymphatic-like vessel formation coupled with abnormal endothelial differentiation and progenitor cell involvement in the neovascularization associated with PDR are novel recent findings which hold potential for improved DR treatment. Understanding the underlying mechanisms of PDR pathogenesis is therefore crucial. To this goal, multidisciplinary approaches and new ex vivo models have been developed for a more comprehensive molecular, cellular and tissue-level understanding of the disease. This is the first step to gain the needed information on how PDR can be better evaluated, stratified, and treated.

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Author Response: Sufficient Evidence for Lymphatics in the Developing and Adult Human Choroid?

Cited by 7 publications

References 22 publications

Unconventional aqueous humor outflow: A review

Unconventional aqueous humor outflow: A review

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

Lymphatic Vascular Structures: A New Aspect in Proliferative Diabetic Retinopathy

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