Abstract
The pathological mechanism underlying retinal apoptosis in X-linked retinoschisis (XLRS), a disease caused by retinoschisin 1 (RS1) deficiency, remains incompletely understood. This study aimed to investigate the role of transient receptor potential melastatin 1 (TRPM1) in retinal tissues and cells. Retinal function and structure were assessed by electroretinography (ERG) and optical coherence tomography (OCT). Protein expression was evaluated by immunofluorescence staining and western blotting (WB). Retinal morphology was examined by hematoxylin and eosin (H&E) staining. Apoptotic retinal cells were detected by TUNEL staining. Key proteins were screened using proteomics data obtained by mass spectrometry. Intracellular calcium levels were measured using Rhod-2 AM. TRPM1 expression in Rs1-KO mice was 1.3-fold higher than that in wild-type mice (p < 0.05), whereas TRPM1-overexpressing ARPE19 cells exhibited approximately twofold higher expression than the empty vector control group. Mechanistically, TRPM1-mediated calcium influx promoted calcium/calmodulin-dependent protein kinase II (CAMKII) phosphorylation. Concomitantly, the accumulation of the autophagy-related proteins P62 and LC3B, increased BAX expression, and decreased BCL2 expression were observed in both Rs1-KO retinal tissues and TRPM1-overexpressing ARPE19 cells. These findings collectively suggest that TRPM1 may contribute to cell’s apoptosis. Our study provides new insight into the mechanism of retinal apoptosis in XLRS.
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Data availability
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the iProX partner repository with the dataset identifier PXD031901.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (No. 82402170, funder: W.P.W.; No. 82271084, funder: B.L.). The Youth Basic Research Project of Henan Eye Hospital (No. 23JCQN001, funder: W.P.W.). The Henan Provincial Medical Science and Technology Tackling Program (No. LHGJ20220087, funder: W.P.W.). Henan Academy of Innovations in Medical Science Eye Institute Applied Research Special Project (No. 20250301, funder: W.P.W.; No. 20250203, funder: X.X.J.). Henan Academy of Innovations in Medical Science Basic Research Operations Program (No.JBKY250311, funder: X.X.J.).
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W.P.W. and B.L. conceived and supervised the study. W.P.W. and J.Y.L. designed the methodology and performed validation experiments. W.P.W. and X.X.J. conducted the formal analysis. W.P.W., M.Z.Y., and R.Q.Q. performed the investigation. S.Y. provided resources. G.M.L. and M.Y.Q. curated the data. W.P.W. wrote the main manuscript text and prepared the figures. B.L. reviewed and edited the manuscript. W.P.W., X.X.J., and B.L. acquired funding. All authors reviewed the manuscript.
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Wang, W., Liu, J., Jin, X. et al. Upregulated TRPM1 is associated with apoptosis in Rs1 knockout mice and in ARPE19 cells through increased intracellular calcium. Sci Rep (2026). https://doi.org/10.1038/s41598-026-47523-5
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DOI: https://doi.org/10.1038/s41598-026-47523-5
