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101. Structural Confirmation of Lymphatic Outflow from Subconjunctival Blebs of Live Human Subjects.

Author

Lee, Jong, Heilweil, Gad, Le, Phuc, Saraswathy, Sindhu, Hong, Young-Kwon, Girkin, Christopher, and Huang, Alex

Subjects
Aqueous Outflow, Blebs, Conjunctiva, Glaucoma Surgery, Lymphatics, Subconjunctival
Abstract

PURPOSE: To uncover the mechanism of subconjunctival outflow in human patients. DESIGN: Cross-sectional study. SUBJECTS/PARTICIPANTS AND/OR CONTROLS: Fifteen subjects receiving subconjunctival anesthesia prior to intravitreal injection for routine clinical care. METHODS: Anterior segment OCT (AS-OCT) was performed in patients with various instances of conjunctival edema or subconjunctival fluid. Other subjects received a subconjunctival mixture of 0.005% indocyanine green and 2% lidocaine. After subconjunctival injection of the tracer/anesthetic mixture, blebs and associated outflow pathways were angiographically imaged and the time for appearance recorded. The pattern and structure of outflow pathways were studied using AS-OCT. Angiographic and AS-OCT results were compared to trabecular/conventional outflow imaging which demonstrates veins. MAIN OUTCOME MEASURES: Ocular surface lymphangiography and AS-OCT images. RESULTS: AS-OCT of the conjunctiva in a normal eye demonstrated thin non-edematous conjunctiva with absent intraconjunctival lumens or subconjunctival fluid. Subjects with a history of trabeculectomy, subconjunctival drug injection, or chemosis demonstrated thickened conjunctiva and intraconjunctival luminal pathways that contained valve-like structures. Tracer-based studies in patients demonstrated blebs with irregular subconjunctival bleb-related outflow patterns that arose in a time-dependent fashion. These angiographic pathways were luminal on OCT, sausage-shaped, and contained intraluminal valve-like structures. This was in contrast to trabecular/conventional outflow imaging where pathways were classically Y-shaped, of even-caliber, and lacked valve-like structures. DISCUSSION: Outflow pathways were seen in cases of conjunctival edema and after subconjunctival tracer injection. These pathways were lymphatic based upon pattern and structural study. Better understanding of bleb-related lymphatic outflow may lead to improved bleb-requiring glaucoma surgeries and subconjunctival drug delivery.

Published
2021

136. Lymphatic Proliferation Ameliorates Pulmonary Fibrosis after Lung Injury.

Author

Baluk, Peter, Naikawadi, Ram P, Kim, Shineui, Rodriguez, Felipe, Choi, Dongwon, Hong, Young-Kwon, Wolters, Paul J, and McDonald, Donald M

Subjects
Macrophages, Lymphatic Vessels, Animals, Mice, Transgenic, Pulmonary Fibrosis, Fibrosis, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor C, Cell Proliferation, Lymphangiogenesis, Lung Injury, Lung, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Respiratory, Medical and Health Sciences, Pathology
Abstract

Despite many reports about pulmonary blood vessels in lung fibrosis, the contribution of lymphatics to fibrosis is unknown. We examined the mechanism and consequences of lymphatic remodeling in mice with lung fibrosis after bleomycin injury or telomere dysfunction. Widespread lymphangiogenesis was observed after bleomycin treatment and in fibrotic lungs of prospero homeobox 1-enhanced green fluorescent protein (Prox1-EGFP) transgenic mice with telomere dysfunction. In loss-of-function studies, blocking antibodies revealed that lymphangiogenesis 14 days after bleomycin treatment was dependent on vascular endothelial growth factor (Vegf) receptor 3 signaling, but not on Vegf receptor 2. Vegfc gene and protein expression increased specifically. Extensive extravasated plasma, platelets, and macrophages at sites of lymphatic growth were potential sources of Vegfc. Lymphangiogenesis peaked at 14 to 28 days after bleomycin challenge, was accompanied by doubling of chemokine (C-C motif) ligand 21 in lung lymphatics and tertiary lymphoid organ formation, and then decreased as lung injury resolved by 56 days. In gain-of-function studies, expansion of the lung lymphatic network by transgenic overexpression of Vegfc in club cell secretory protein (CCSP)/VEGF-C mice reduced macrophage accumulation and fibrosis and accelerated recovery after bleomycin treatment. These findings suggest that lymphatics have an overall protective effect in lung injury and fibrosis and fit with a mechanism whereby lung lymphatic network expansion reduces lymph stasis and increases clearance of fluid and cells, including profibrotic macrophages.

Published
2020

139. Decadal Changes in the Antarctic Sea Ice Response to the Changing ENSO in the Last Four Decades

Author

Young-Kwon Lim, Dong L. Wu, Kyu-Myong Kim, and Jae N. Lee

Subjects
Meteorology and Climatology, Earth Resources and Remote Sensing
Abstract

Sea ice fraction (SIF) over the Ross/Amundsen/Bellingshausen Sea (RAB) are investigated using the Modern-Era Retrospective Analysis for Research and Application, Version 2 (MERRA-2), focusing on the differences in time-lagged response to ENSO between the late 20th (1980–2000, L20) and the early 21st century (2001–2021, E21). The findings suggest that the typical Antarctic response to ENSO is influenced by changes in ENSO type/intensity, highlighting the need for caution when investigating the Antarctic teleconnection. Time-lagged regressions onto the mature phase of El Niño reveal that the SIF decrease and SST increase over the RAB is relatively weaker in E21 and most pronounced at 0–4 months lag. Conversely, the SIF in L20 continues to decline and reaches its peak at two-season lag (5–7 months). Tropospheric wind, pressure, and wave activity in response to El Niño in L20 show a zonally oriented high/low-pressure areas with two-season lag, enhancing the poleward flow that plays a key role in sea ice melt in the RAB, while this pattern in E21 is insignificant at the same lag. This study suggests that stronger (weaker) and more eastern (central) Pacific ENSOs on average in L20 (E21) are associated with this decadal change in the SIF response to ENSO.

Published
2023
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150. North American extreme precipitation events and related large-scale meteorological patterns: a review of statistical methods, dynamics, modeling, and trends

Author

Barlow, Mathew, Gutowski, William J, Gyakum, John R, Katz, Richard W, Lim, Young-Kwon, Schumacher, Russ S, Wehner, Michael F, Agel, Laurie, Bosilovich, Michael, Collow, Allison, Gershunov, Alexander, Grotjahn, Richard, Leung, Ruby, Milrad, Shawn, and Min, Seung-Ki

Subjects
Climate Action, Atmospheric Sciences, Oceanography, Physical Geography and Environmental Geoscience, Meteorology & Atmospheric Sciences
Abstract

This paper surveys the current state of knowledge regarding large-scale meteorological patterns (LSMPs) associated with short-duration (less than 1 week) extreme precipitation events over North America. In contrast to teleconnections, which are typically defined based on the characteristic spatial variations of a meteorological field or on the remote circulation response to a known forcing, LSMPs are defined relative to the occurrence of a specific phenomenon—here, extreme precipitation—and with an emphasis on the synoptic scales that have a primary influence in individual events, have medium-range weather predictability, and are well-resolved in both weather and climate models. For the LSMP relationship with extreme precipitation, we consider the previous literature with respect to definitions and data, dynamical mechanisms, model representation, and climate change trends. There is considerable uncertainty in identifying extremes based on existing observational precipitation data and some limitations in analyzing the associated LSMPs in reanalysis data. Many different definitions of “extreme” are in use, making it difficult to directly compare different studies. Dynamically, several types of meteorological systems—extratropical cyclones, tropical cyclones, mesoscale convective systems, and mesohighs—and several mechanisms—fronts, atmospheric rivers, and orographic ascent—have been shown to be important aspects of extreme precipitation LSMPs. The extreme precipitation is often realized through mesoscale processes organized, enhanced, or triggered by the LSMP. Understanding of model representation, trends, and projections for LSMPs is at an early stage, although some promising analysis techniques have been identified and the LSMP perspective is useful for evaluating the model dynamics associated with extremes.

Published
2019

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