Biology subjects

Choy, K.

Publications and source records attributed to Choy, K..

3 recordsLinked to original sources

bioRxiv2023

Aging and intraocular pressure homeostasis in mice

Age and elevated intraocular pressure (IOP) are the two primary risk factors for glaucoma, an optic neuropathy that is the leading cause of irreversible blindness. In most people, IOP is tightly regulated over a lifetime by the conventional outflow tissues. However, the mechanistic contributions of age to conventional outflow dysregulation, elevated IOP and glaucoma are unknown. To address this gap in knowledge, we studied how age affects the morphology, biomechanical properties and function of conventional outflow tissues in C57BL/6 mice, which have an outflow system similar to humans. As reported in humans, we observed that IOP in mice was maintained within a tight range over their lifespan. Remarkably, despite a constellation of age-related changes to the conventional outflow tissues that would be expected to hinder aqueous drainage and impair homeostatic function (decreased cellularity, increased pigment accumulation, increased cellular senescence and increased stiffness), outflow facility, a measure of conventional outflow tissue fluid conductivity, was stable with age. We conclude that the murine conventional outflow system has significant functional reserve in healthy eyes. However, these age-related changes, when combined with other underlying factors, such as genetic susceptibility, are expected to increase risk for ocular hypertension and glaucoma.

physiology↗

bioRxiv2022

Turicibacter modifies host bile acids and lipids in a strain-specific manner

Bacteria from the Turicibacter genus are prominent members of the mammalian gut microbiota and are associated with alterations in dietary fat and body weight, but the specific connections between these symbionts and host physiology are poorly understood. We genomically and phenotypically characterized a diverse set of mouse-and human-derived Turicibacter strains, and found they group into three clades that differ in their transformations of bile acids. We identified Turicibacter bile salt hydrolases that confer strain-specific differences in bile deconjugation. Colonization with individual Turicibacter strains led to changes in host bile acid profiles, generally aligning with those produced in vitro. Further, colonizing mice with another bacterium expressing bile-modifying genes from these strains decreased serum cholesterol and triglycerides, as well as adipose tissue mass. This work identifies genes that enable diverse Turicibacter strains to differentially modify host bile acids and lipid metabolism, and positions multiple Turicibacter strains as candidates for altering host fat biology. MAIN TEXT

microbiology↗

bioRxiv2021

A novel hybrid protein promotes Aβ clearance and reduces inflammatory response through MerTK

Alzheimers disease (AD) is the worlds leading cause of dementia and the most common neurodegenerative disorder. Its major pathological features are amyloid beta (A{beta}) plaques, tau tangles, and neuroinflammation that eventually leads to massive death of nerve cells. Even with the multifactorial aspect of AD, the most accepted theory is that A{beta} is the driving force of AD pathogenesis. We engineered a novel hybrid protein that facilitates the phagocytosis of A{beta} and redirect its clearance to the noninflammatory Mer tyrosine kinase (MerTK) pathway. The novel hybrid protein facilitates robust uptake and clearance of A{beta} in BV2 microglia through MerTK receptor with reduced production of inflammatory factors and oxidative products. In APP/PS1 transgenic AD mouse model, intraperitoneal administration of the hybrid protein for two months results in significant reduction of A{beta} burden in the brain and protection of nerve cells from dying. Taken together, our results suggest that the novel hybrid may have the potential for AD treatment by targeting both A{beta} clearance and reduction of inflammation.

molecular biology↗