Biology subjects

Telias, M.

Publications and source records attributed to Telias, M..

3 recordsLinked to original sources

bioRxiv2026

The P2X7 receptor is an intermediate in the retinoic acid-signaling pathway that induces neuronal remodeling in retinitis pigmentosa

Photoreceptor degeneration drives electrophysiological remodeling in downstream retinal neurons, including hyperactive firing of retinal ganglion cells (RGCs) that degrades residual vision. Although Retinoic Acid (RA) and its receptor (RAR) are known to upregulate ion channel genes associated with RGC hyperactivity, these genes lack canonical RAR binding sites required for direct transcriptional regulation. Here, we identify P2X7 receptor (P2X7R) as a key intermediary in RA-induced remodeling in the rd1 mouse model of retinitis pigmentosa. Genetic deletion of P2X7R prevents the upregulation of RA-responsive genes and abolishes RGC hyperactivity. Loss of P2X7R also eliminates RGC hyperpermeability, as measured by uptake of an otherwise membrane-impermeant dye. Acute pharmacological inhibition of P2X7R suppresses hyperpermeability without affecting hyperactivity, supporting an indirect signaling mechanism rather than a direct electrophysiological role. Notably, elevation of resting Ca{superscript 2} is absent in P2X7R-deficient cells, implicating Ca{superscript 2}-dependent gene expression as a link between P2X7R-mediated hyperpermeability and RGC hyperactivity. Together, these findings establish P2X7R as a critical intermediate in retinal remodeling and a potential therapeutic target for preserving vision in retinitis pigmentosa. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/728267v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@7745d4org.highwire.dtl.DTLVardef@89a01corg.highwire.dtl.DTLVardef@16ea51borg.highwire.dtl.DTLVardef@119d0f9_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Inhibiting retinoic acid mitigates vision loss in a mouse model of retinal degeneration

In degenerative retinal disorders, rod and cone photoreceptors die, causing vision impairment and blindness. Downstream neurons survive but undergo morphological and physiological remodeling, with some retinal ganglion cells (RGC) exhibiting heightened spontaneous firing. Retinoic acid (RA) has been implicated as the key signaling molecule that induces RGC hyperactivity, obscuring RGC light responses and reducing light avoidance behaviors triggered by residual rods and cones. However, evidence that RA-dependent remodeling corrupts image-forming vision has been lacking. Here we show that disulfiram, an FDA-approved drug that inhibits RA synthesis, and BMS 493, an RA receptor (RAR) inhibitor, reduce RGC hyperactivity and augment image detection in visually impaired mice. Functional imaging of visual cortical neurons shows that disulfiram and BMS 493 sharpen orientation-tuning and strengthen response fidelity to naturalistic scenes. These findings establish a causal link between RA-induced retinal hyperactivity and vision impairment and define molecular targets and candidate drugs for boosting image-forming vision in retinal degeneration.

neuroscience↗

bioRxiv2019

Neural differentiation is increased by GSK-3β inhibition and decreased by tankyrase inhibition in human neural precursor cells

Glycogen synthase kinase-3{beta} (GSK-3{beta}) and tankyrase-1/2 (TANK) are two enzymes known to play multiple roles in cell biology, including regulation of proliferation, differentiation and metabolism. Both of them act on the canonical Wnt/{beta}-Catenin pathway, but are also involved in many other independent intracellular mechanisms. More importantly, GSK-3{beta} and TANK have been shown to play crucial roles in different diseases, including cancer and neurological disorders. The GSK-3{beta}-inhibitor CHIR and the TANK-inhibitor XAV are two pyrimidine molecules, holding high potential as possible therapeutic drugs. However, their effect on neural tissue is poorly understood. In this study, we tested the effects of CHIR and XAV on human neural precursor cells (hNPCs) derived from human embryonic stem cells. We found that CHIR-mediated inhibition of GSK-3{beta} promotes neural differentiation. In contrast, XAV-mediated inhibition of TANK leads to de-differentiation. These results highlight the relative importance of these two enzymes in determining the neurodevelopmental status of hNPCs. Furthermore, they shed light on the roles of Wnt signaling during early human neurogenesis.

cell biology↗