Biology subjects

Kusk, P.

Publications and source records attributed to Kusk, P..

3 recordsLinked to original sources

bioRxiv2025

Functional and structural profiling of circulation via genetically encoded modular fluorescent probes.

Sustained labeling of fluids is crucial for their investigation in animal models. Here, we introduce a mouse line (Alb-mSc-ST), where blood and interstitial fluid are labeled with the red fluorescent protein mScarlet and SpyTag. The SpyTag-SpyCatcher technology is exploited to monitor circulating fluid properties by biosensors or detect blood-brain barrier disruption. This approach represents a valuable tool for studying vascular structure, permeability and microenvironment in body organs in vivo.

neuroscience↗

bioRxiv2022

Liver-secreted fluorescent blood plasma markers enable chronic imaging of microcirculation

Studying blood microcirculation is vital for gaining insights into vascular diseases. Acute administration of fluorescent tracers is currently used for deep tissue blood flow imaging. This is invasive, and the plasma fluorescence decreases within an hour of administration. We report a novel approach for the longitudinal study of vasculature. Using a single systemic administration of viral vectors, we express fluorescent secretory albumin-fusion proteins in the liver to label the blood in mice. All segments of the vasculature in brain and peripheral tissue are observable by two-photon microscopy within two weeks of vector administration. This approach allows for observation of circulation without the need for repeated administration for several months. We demonstrate the chronic assessment of vascular functions at micro-and mesoscopic scales. This genetic plasma labeling approach represents a versatile and cost-effective method for the chronic investigation of vasculature functions across the body in health and disease.

physiology↗

bioRxiv2019

The Ocular Glymphatic Clearance System

Despite high metabolic activity, the retina and optic nerve head lack traditional lymphatic drainage. We here identified a novel ocular glymphatic clearance route for fluid and wastes via the proximal optic nerve. Amyloid-{beta} (A{beta}) was cleared from the vitreous via a pathway driven by the ocular-cranial pressure difference. After traversing the lamina barrier, intra-axonal A{beta} was cleared via the perivenous space and subsequently drained to lymphatic vessels. Light-induced pupil constriction enhanced, while atropine or raising intracranial pressure blocked efflux. In two distinct murine models of glaucoma, A{beta} leaked from the eye via defects in the lamina barrier instead of directional axonal efflux. The discovery of a novel pathway for removal of fluid and metabolites from the intraocular space prompts a reevaluation of the core principles governing eye physiology and provides a framework for new therapeutic approaches to treat common eye diseases, including glaucoma. One Sentence SummaryGlymphatic pathway clears ocular amyloid-{beta} via optic nerve and fails in glaucoma.

physiology↗