Invariant asymmetry renews the lymphatic vasculature during homeostasis.

Background: The lymphatic vasculature regulates tissue physiology and immunity throughout life. The self renewal mechanism that maintains the lymphatic vasculature during conditions of homeostasis is unknown. The purpose of this study was to investigate the cellular mechanism of lymphatic endothelial cell (LEC) self renewal and lymphatic vessel maintenance.

Lymphatic endothelial lineage assemblage during corneal lymphangiogenesis.

Postnatal inflammatory lymphangiogenesis presumably requires precise regulatory processes to properly assemble proliferating lymphatic endothelial cells (LECs). The specific mechanisms that regulate the assembly of LECs during new lymphatic vessel synthesis are unclear. Dynamic endothelial shuffling and rearrangement has been proposed as a mechanism of blood vessel growth.

Nerve growth factor regulates neurolymphatic remodeling during corneal inflammation and resolution.

The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation-pain and swelling-by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo.

Calcium regulates molecular interactions of otoferlin with soluble NSF attachment protein receptor (SNARE) proteins required for hair cell exocytosis.

Mutations in otoferlin, a C2 domain-containing ferlin family protein, cause non-syndromic hearing loss in humans (DFNB9 deafness). Furthermore, transmitter secretion of cochlear inner hair cells is compromised in mice lacking otoferlin. In the present study, we show that the C2F domain of otoferlin directly binds calcium (KD = 267 μM) with diminished binding in a pachanga (D1767G) C2F mouse mutation.

Lymphatic vessel memory stimulated by recurrent inflammation.

Inflammation stimulates new lymphatic vessel growth (inflammatory lymphangiogenesis). One key question is how recurrent inflammation, a common clinical condition, regulates lymphatic vessel remodeling. We show here that recurrent inflammation accelerated the development a functional lymphatic vessel network.

Glucocorticoids suppress corneal lymphangiogenesis.

Purpose: To determine whether glucocorticoids suppress corneal lymphatic vessel growth (lymphangiogenesis) or induce lymphatic vessel regression.

Methods: We measured human lymphatic endothelial cell proliferation and collagen-induced tubulogenesis in culture conditions with and without dexamethasone, a potent glucocorticoid. We developed a modification of the mouse corneal suture model that allowed us to visualize lymphatic vessel growth (with suture) or regression (suture removed) using immunofluorescence and microscopic techniques.

Regressed lymphatic vessels develop during corneal repair.

The fate of newly synthesized lymphatic vessels induced by inflammation is poorly understood. To address this question, we designed experiments to determine the morphologic, phenotypic, and functional differences in regressing lymphatic vessels in the context of corneal recovery after an inflammatory response. A suture removal modification was used to induce corneal recovery after suture induced inflammation.

β1 integrin regulates MMP-10 dependant tubulogenesis in human lymphatic endothelial cells.

Lymphatic vessel growth requires extensive remodeling of the extracellular matrix, a process hypothesized to be related to the expression and function of the matrix metalloproteinases. We used a protein based screening strategy to demonstrate increased matrix matalloproteinase-10 expression in human lymphatic endothelial cells undergoing collagen I induced tubulogenesis. Knock-down experiments showed that matrix metalloproteinase-10 regulated lymphatic endothelial cell tubulogenesis.

Lymphatic vessel hypertrophy in inflamed human tonsils.

The structural and molecular properties of the human tonsil lymphatic microvascular system are important to understand as these features likely contribute to fluid balance, immunity, and tumor metastasis. The tonsil is a unique lymphoid organ in that it is in intimate contact with the contents of the upper aerodigestive tract and that there are no identifiable afferent lymphatics. Conventional immunofluorescence microscopy demonstrated a remarkable degree of lymphatic vessel architecture within the tonsil; LYVE-1-positive lymphatic vessels were detected around each germinal center and in the marginal regions between the follicles.

Is hearing loss due to mutations in the Connexin 26 gene progressive?

Serial audiograms were analysed for seven subjects, who were homozygous for the 35delG GJB2 mutation. The criterion for determining progression of hearing loss was at least a 1-dB loss in air conduction pure-tone average-3 (ACPTA-3) or ACPTA-4 per year for 2 to 10 years, with a minimum change of 10 dB ACPTA 3 or 4. Bilateral progression of hearing loss was found in 43% (3/7) of the subjects.

GJB2 mutations and degree of hearing loss: a multicenter study.

Hearing impairment (HI) affects 1 in 650 newborns, which makes it the most common congenital sensory impairment. Despite extraordinary genetic heterogeneity, mutations in one gene, GJB2, which encodes the connexin 26 protein and is involved in inner ear homeostasis, are found in up to 50% of patients with autosomal recessive nonsyndromic hearing loss. Because of the high frequency of GJB2 mutations, mutation analysis of this gene is widely available as a diagnostic test.

Searching for evidence of DFNB2.

Deafness is the most common form of sensory impairment in humans, affecting about 1 in 1,000 births in the United States. Of those cases with genetic etiology, approximately 80% are nonsyndromic and recessively inherited. Mutations in several unconventional myosins, members of a large superfamily of actin-associated molecular motors, have been found to cause hearing loss in both humans and mice.