{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T21:34:30Z","timestamp":1787693670523,"version":"build-2784847793"},"reference-count":61,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:00:00Z","timestamp":1694995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["31003A_176065"],"award-info":[{"award-number":["31003A_176065"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Loss of photoreceptors in retinal degenerative diseases also impacts the inner retina: bipolar cell dendrites retract, neurons rewire, and protein expression changes. ON-bipolar cells (OBCs) represent an attractive target for optogenetic vision restoration. However, the above-described maladaptations may negatively impact the quality of restored vision. To investigate this question, we employed human post-mortem retinas and transgenic rd1_Opto-mGluR6 mice expressing the optogenetic construct Opto-mGluR6 in OBCs and carrying the retinal degeneration rd1 mutation. We found significant changes in delayed rectifier potassium channel expression in OBCs of degenerative retinas. In particular, we found an increase in Kv1.3 expression already in early stages of degeneration. Immunohistochemistry localized Kv1.3 channels specifically to OBC axons. In whole-cell patch-clamp experiments, OBCs in the degenerated murine retina were less responsive, which could be reversed by application of the specific Kv1.3 antagonist Psora-4. Notably, Kv1.3 block significantly increased the amplitude and kinetics of Opto-mGluR6-mediated light responses in OBCs of the blind retina and increased the signal-to-noise ratio of light-triggered responses in retinal ganglion cells. We propose that reduction in Kv1.3 activity in the degenerated retina, either by pharmacological block or by KCNA3 gene silencing, could improve the quality of restored vision.<\/jats:p>","DOI":"10.3390\/ijms241814207","type":"journal-article","created":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T23:57:46Z","timestamp":1694995066000},"page":"14207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Selective Block of Upregulated Kv1.3 Potassium Channels in ON-Bipolar Cells of the Blind Retina Enhances Optogenetically Restored Signaling"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2121-9920","authenticated-orcid":false,"given":"Giulia","family":"Schilardi","sequence":"first","affiliation":[{"name":"Institute of Physiology & Department of Biomedical Research (DBMR), Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5216-9818","authenticated-orcid":false,"given":"Jakub","family":"Kralik","sequence":"additional","affiliation":[{"name":"Institute of Physiology & Department of Biomedical Research (DBMR), Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8272-7833","authenticated-orcid":false,"given":"Sonja","family":"Kleinlogel","sequence":"additional","affiliation":[{"name":"Institute of Physiology & Department of Biomedical Research (DBMR), Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8936","DOI":"10.1523\/JNEUROSCI.18-21-08936.1998","article-title":"The Major Cell Populations of the Mouse Retina","volume":"18","author":"Jeon","year":"1998","journal-title":"J. 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