Biology subjects

Li, H.-L.

Publications and source records attributed to Li, H.-L..

6 recordsLinked to original sources

bioRxiv2026

VEGFA-Positive Macrophages Regulate Aqueous Humor Outflow in Aged Mice and Humans

Elevated intraocular pressure (IOP) and aging are major risk factors for primary open-angle glaucoma (POAG), but how aging affects IOP regulation remains poorly understood. IOP remains within a narrow range despite age-associated changes predicted to increase aqueous humor outflow (AHO) resistance at the interface between the trabecular meshwork and Schlemm's canal (SC), suggesting compensatory mechanisms preserve AHO homeostasis during aging. Single-cell RNA sequencing of mouse ocular angle tissues revealed immunomodulatory transcriptional reprogramming of SC endothelial cells in older mice, while mouse and human imaging showed reduced SC size and increased peri-SC macrophage accumulation with aging. Ligand-receptor analysis predicted enhanced macrophage-to-SC VEGFA-VEGFR signaling in aged and Tie2-haploinsufficient mice, an independent model of vascular stress and glaucoma risk. Deletion of Vegfa in CX3CR1+ macrophages increased IOP and reduced AHO facility in 9-month-old mice, demonstrating that macrophage-derived VEGFA supports AHO homeostasis. Tie2 haploinsufficiency recapitulated key age-associated SC niche changes, including peri-SC macrophage accumulation, whereas gene therapy boosting TIE2 activity protected wild-type mice against age-related changes. Together, these findings identify peri-SC macrophage-derived VEGFA as a compensatory mechanism maintaining AHO homeostasis during aging and vascular stress and support TIE2 activation as a therapeutic strategy to preserve SC function and IOP regulation.

physiology↗

bioRxiv2026

Endothelin 2-Mediated Neuroinflammation Drives Hypertension-Associated Retinal Dysfunction

Systemic hypertension is a significant risk factor for glaucoma, a leading cause of irreversible blindness, yet the mechanistic basis connecting the two conditions remains elusive. Here, we demonstrate that hypertensive rats develop accelerated retinal degeneration characterized by retinal thinning, functional impairment, reduced perfusion, and progressive neuroinflammation. Critically, these changes occur despite persistently lower intraocular pressure (IOP), indicating an IOP-independent mechanism of pathology. Transcriptomic and biochemical analyses identified a robust activation of the retinal endothelin system, with endothelin-2 (EDN2) being the earliest and most significantly upregulated component. AAV-delivered retinal Edn2 knockdown completely restored retinal function, ameliorated neuroinflammation, and enhanced retinal blood flow in hypertensive rats. Pharmacological blockade of endothelin receptor type A (EDNRA), but not type B, replicated these protective effects without altering IOP. Our findings establish EDN2 as a central, IOP-independent driver of hypertension-associated retinal neurodegeneration and identify the endothelin-EDNRA axis as a potential therapeutic target to prevent vision loss in hypertensive patients.

neuroscience↗

bioRxiv2026

Schizosaccharomyces orthogroup (SOG) resource: a web platform for exploring gene conservation in fission yeasts

The fission yeast Schizosaccharomyces pombe is a prominent model organism widely used to investigate fundamental cellular mechanisms. In addition to S. pombe, the genus Schizosaccharomyces includes six other species--S. octosporus, S. japonicus, S. cryophilus, S. osmophilus, S. lindneri, and S. versatilis. These fission yeast species share a common ancestor from which the genus diversified over more than 200 million years. This extensive evolutionary divergence provides opportunities for comparative genomics. Here, we present the Schizosaccharomyces orthogroup (SOG) resource, a web platform developed from our high-quality genome assemblies, gene annotations, and orthology assignments. Most fission yeast genes are assigned to one of over 5,000 orthogroups. The platform enables users to visualize orthogroup sequence alignments and phylogenetic trees, retrieve coding and flanking sequences, and explore the conservation of local synteny. This resource will benefit researchers focusing on individual genes as well as those investigating gene evolution at broader scales. It is freely accessible at https://www.sogweb.org. TAKE AWAYO_LIThe SOG resource covers all known species of Schizosaccharomyces. C_LIO_LIThe platform is built on high-quality genome assemblies and annotations. C_LIO_LIMost genes are assigned to one of over 5,000 orthogroups. C_LIO_LIUsers can view and explore alignments, phylogenetic trees, and local synteny. C_LIO_LIThis free resource aids functional and evolutionary research. C_LI

genomics↗

bioRxiv2025

Artificial light at night and an invasive snail synergistically enhance the invasion of a non-native macrophyte

Herbivory shapes plant invasion outcomes, yet its role in aquatic plant invasions under changing environmental conditions, such as artificial light at night (ALAN), remains poorly understood. We conducted three experiments using invasive macrophyte Myriophyllum aquaticum, a native macrophyte community (Vallisneria natans, Hydrilla verticillata, M. spicatum), invasive snail Pomacea canaliculata, and native snail Cipangopaludina chinensis to test the combined effects of ALAN and herbivory on non-native macrophyte invasions. ALAN increased M. aquaticum height and total biomass, but had no effect on native species growth. In feeding assays, P. canaliculata consumed all three native species but consistently avoided M. aquaticum under both light treatments. C. chinensis showed no feeding in no-choice assays, but in choice assays, consumed H. verticillata and M. spicatum under No-ALAN and only M. spicatum under ALAN. In community mesocosms, P. canaliculata reduced native macrophyte biomass by 48.0% under No-ALAN and 87.2% under ALAN without affecting M. aquaticum. This selective feeding increased M. aquaticums proportional biomass, with a stronger effect under ALAN than No-ALAN. These results suggest that ALAN can indirectly facilitate non-native macrophyte invasion by amplifying their relative biomass within native communities, particularly in the presence of invasive herbivores, and may promote invasional meltdown through altered feeding preferences.

ecology↗

bioRxiv2025

A New Pathway for the Decussation of Corticospinal Tracts

Each brain hemisphere controls the movements of the opposite side of the body because the motor axons cross the midline, known as CST decussation. The current theory on CST decussation suggests CSTs decussate as a single tract at the junction between medulla and spinal cord. Although this theory is widely accepted, this theory is based on selective analyses and is therefore incomplete. Here, we employed new approaches, including the horizontal analyses and a non-invasive anterograde tracing method to examine CST decussation thoroughly. We analyzed all CS axons in 3 planes. These approaches led to the discovery of a new pathway for CST decussation. We found CSTs turned back to medulla, moving anteriorly and decussated in an oval structure. In this structure, each CST split into 4 fascicle groups and interdigitated with the corresponding groups from the opposite CST to cross the midline. The significance of this pathway was apparent after decussation where these 4 groups reversed direction, moving posteriorly toward spinal cord. While moving, the motor axons gradually separated at different locations and subsequently turned and occupied the correct positions in the dorsal funiculus for proper limb control. In addition to CSTs, we also characterized several components in the oval structure.

neuroscience↗

bioRxiv2024

Antibodies against the capsid induced after intracranial AAV administration limits second administration in a dose dependent manner

Recombinant adeno-associated virus (rAAV) is a widely used viral vector for gene therapy. However, a limitation of AAV-mediated gene therapy is that patients are typically dosed only once. In this study, we investigated the possiblility to deliver multiple rounds of AAV through intracerebral injections in the mouse brain. We discovered a dose-dependent modulation of the second round AAV infection by the first round AAV injection in the brain-wide scales besides the injection region. High-dose AAV infection increases chemokines CXCL9 and CXCL10 to recruit the parenchymal infiltration of lymphocytes. Surprisingly, the blood-brain-barrier was relatively intact. Brain-wide dissection discovered the likely rountes of the infiltrated lymphocytes through perivascular space and ventricles. Further analysis using B-cell depleted mice revealed that B lymphocytes, but not T lymphocytes, played a critical role in inhibiting the second round AAV infection. Strategies against neutralizing antibodies had limited effects, while reducing the dosage for the first injection or switching the second AAV to a different serotype appeared to be more effective in antagonizing the first round AAV inhibition. Together, these results suggest that mammalian brains are not immunoprivileged for AAV infection, but multiple rounds of AAV gene therapy are still possible if designed carefully with proper doses and serotypes.

immunology↗