Sphingosine-1-phosphate signaling through Müller glia regulates neuroprotection and the accumulation of immune cells in the rodent retina DOI Creative Commons

Olivia Taylor,

Lisa E. Kelly,

Heithem M. El‐Hodiri

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 6, 2025

Abstract The purpose of this study was to investigate how Sphingosine-1-phosphate (S1P) signaling regulates glial phenotype, neuroprotection, and reprogramming Müller glia (MG) into neurogenic MG-derived progenitor cells (MGPCs) in the adult mouse retina. We found that S1P-related genes were dynamically regulated following retinal damage. S1pr1 (encoding S1P receptor 1) Sphk1 sphingosine kinase are expressed at low levels by resting MG rapidly upregulated acute Overexpression bHLH transcription factor Ascl1 downregulates , inhibition S1pr1/3 enhances Ascl1-driven differentiation bipolar-like suppresses differentiation. Treatments activate or increase initiate pro-inflammatory NFκB-signaling MG, whereas treatments inhibit decreased suppress damaged retinas. Conditional knock-out increases expression but decreases S1pr3 . (cKO) not accumulation immune acutely cKO i s neuroprotective ganglion cells, is amacrine NMDA-damaged Consistent with these findings, pharmacological receptors had protective effects upon inner neurons. conclude S1P-signaling pathway activated after damage acts secondarily restrict impairs neuron survival progenitors

Язык: Английский

Sphingosine-1-phosphate signaling through Müller glia regulates neuroprotection and the accumulation of immune cells in the rodent retina DOI Creative Commons

Olivia Taylor,

Lisa E. Kelly,

Heithem M. El‐Hodiri

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 6, 2025

Abstract The purpose of this study was to investigate how Sphingosine-1-phosphate (S1P) signaling regulates glial phenotype, neuroprotection, and reprogramming Müller glia (MG) into neurogenic MG-derived progenitor cells (MGPCs) in the adult mouse retina. We found that S1P-related genes were dynamically regulated following retinal damage. S1pr1 (encoding S1P receptor 1) Sphk1 sphingosine kinase are expressed at low levels by resting MG rapidly upregulated acute Overexpression bHLH transcription factor Ascl1 downregulates , inhibition S1pr1/3 enhances Ascl1-driven differentiation bipolar-like suppresses differentiation. Treatments activate or increase initiate pro-inflammatory NFκB-signaling MG, whereas treatments inhibit decreased suppress damaged retinas. Conditional knock-out increases expression but decreases S1pr3 . (cKO) not accumulation immune acutely cKO i s neuroprotective ganglion cells, is amacrine NMDA-damaged Consistent with these findings, pharmacological receptors had protective effects upon inner neurons. conclude S1P-signaling pathway activated after damage acts secondarily restrict impairs neuron survival progenitors

Язык: Английский

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