Prentiss, M. | Search bioRxiv

bioRxiv2026

Angiopoietin-like protein 7 (ANGPTL7)-mediated effects on resident immune cells contribute to neurodegeneration in glaucomatous optic nerve head

Glaucoma is an optic neuropathy characterized by progressive retinal degeneration. Population genetic analyses describe an association of variants in angiopoietin-like protein 7 (ANGPTL7) with lower intraocular pressure (IOP) and decreased glaucoma susceptibility. In addition to its reported role in the trabecular meshwork (TM), we demonstrate that ANGPTL7 is also expressed within disease-relevant cell types of the human posterior eye, specifically prelaminar optic nerve head astrocytes (ONHA). Contrasting with previously published findings, we observe no difference in IOP between Angptl7-/- mice and wild-type littermates. Despite absence of an IOP phenotype, loss of ANGPTL7 protects from IOPinduced retinal ganglion cell (RGC) damage in a rodent glaucoma neurodegeneration model. ANGPTL7 may signal through LAIR1-positive immune cells, potentially contributing to pro-inflammatory signaling and phenotypic modulation of resident immune cells, with evidence suggesting that oligomerization of ANGPTL7 is necessary for its activity. Comprehensively, our data highlight an unappreciated role of ANGPTL7 in modulating neuroinflammation in the posterior eye, contributing to glaucoma progression.

neuroscience↗

bioRxiv2026

Mechanical response of the RecA nucleoprotein filament to increasing D-loop length

AO_SCPLOWBSTRACTC_SCPLOWProtein filaments play fundamental functions in the cell, ranging from scaffolding like in the cytoskeleton to sensing and transmitting forces and torques. Here we address the case of the nucleoprotein filaments (NPFs) of homologous recombination (HR) formed by the polymerization of the RecA protein on DNA. In contrast to the cytoskeleton filaments, the HR filaments are not known to exert or sense forces. However the stress in the stretched and unwound DNA bound to those filaments was shown to play a role in promoting DNA strand exchange during the early stage of the HR mechanism. Here we use molecular dynamics simulations to examine whether the strain in the nucleoprotein filament upon strand exchange progression and D-loop formation may influence subsequent steps of the HR process. Our results indicate that the filament mechanical properties are sensitive to the length of DNA incorporated in the D-loop. The response we observe upon increasing the D-loop length is first elastic, up to a threshold that we estimate to be 27 incorporated base pairs, after which the NPF enters a new stage where the protein-DNA connectivities are reorganized. Notably, the DNA displaced strand locally switches from site II to site III, a newly characterized binding site. We discuss the possible consequence of this mechanical response of the NPFs for the course of the HR process.

molecular biology↗