{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:15:26Z","timestamp":1785428126022,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,13]]},"group-title":"Neuroscience","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["EY031312"],"award-info":[{"award-number":["EY031312"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Optogenetics is emerging as a powerful approach for partial vision restoration, with at least three ongoing clinical trials in humans testing novel light-sensitive proteins (opsins) in patients with inherited retinal degenerative disorders. These therapies aim to restore light responsiveness by introducing opsins into surviving retinal cells, such as bipolar or ganglion cells, enabling them to generate neural activity in response to visual stimuli. One ongoing difficulty in selecting promising opsins for clinical development is that there is no way to predict patient perceptual outcomes from optogenetically evoked neural activity as measured\n                  <jats:italic>ex vivo<\/jats:italic>\n                  . Here, we introduce a\n                  <jats:italic>virtual patient<\/jats:italic>\n                  framework that quantitatively links the sensitivity and speed of opsin-mediated retinal responses to predicted patient outcomes, and show how this framework can predict temporal contrast sensitivity functions - a well-established measure of perceptual performance - from microbial opsin photocurrent responses. Our simulations demonstrate that opsin sensitivity and kinetics jointly determine perceptual outcomes, and that enhancing sensitivity at the expense of temporal resolution can degrade the perception of fast-moving stimuli. This computational platform provides a generalizable tool for comparing and selecting the most effective opsins for clinical translation, thereby guiding the design and optimization of next-generation sight restoration strategies.\n                <\/jats:p>","DOI":"10.64898\/2026.04.09.716230","type":"posted-content","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T19:35:12Z","timestamp":1776108912000},"source":"Crossref","is-referenced-by-count":0,"title":["Using Virtual Patients to Predict Perceptual Outcomes for Optogenetic Sight Recovery Technologies"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0459-1982","authenticated-orcid":false,"given":"Vaishnavi B","family":"Mohan","sequence":"first","affiliation":[{"name":"Department of Psychology, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9768-9649","authenticated-orcid":false,"given":"Ezgi Irmak","family":"Yucel","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0142-7239","authenticated-orcid":false,"given":"Ione","family":"Fine","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6561-6920","authenticated-orcid":false,"given":"Geoffrey","family":"Boynton","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041606200844000_2026.04.09.716230v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(13)70145-1"},{"key":"2026041606200844000_2026.04.09.716230v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1525"},{"key":"2026041606200844000_2026.04.09.716230v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.02.026"},{"key":"2026041606200844000_2026.04.09.716230v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01351-4"},{"issue":"5","key":"2026041606200844000_2026.04.09.716230v1.5","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1016\/j.ymthe.2025.03.031","article-title":"A synthetic opsin restores vision in patients with severe retinal degeneration","volume":"33","year":"2025","journal-title":"Molecular Therapy"},{"key":"2026041606200844000_2026.04.09.716230v1.6","unstructured":"GenSight Biologics. A Phase 1\/2a, Open-Label, Non-Randomized, Dose-Escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa. Clinical trial registration NCT03326336, clinicaltrials.gov, July 2022. submitted: 2017-10-11."},{"key":"2026041606200844000_2026.04.09.716230v1.7","unstructured":"Bionic Sight LLC. Phase 1\/2, Safety and Efficacy Trial of BS01, a Recombinant Adeno-Associated Virus Vector Expressing ChronosFP in Patients With Retinitis Pigmentosa. Clinical trial registration NCT04278131, clinicaltrials.gov, May 2023. submitted: 2020-02-13."},{"issue":"8","key":"2026041606200844000_2026.04.09.716230v1.8","first-page":"5443","article-title":"Efficacy and safety of MCO-010 optogenetic therapy for vision restoration in patients with severe vision loss due to retinitis pigmentosa: A phase 2b randomized, sham-controlled, multi-center, multi-dose, double-masked clinical trial (RESTORE)","volume":"64","year":"2023","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"2026041606200844000_2026.04.09.716230v1.9","unstructured":"Nanoscope Therapeutics Inc. A Phase 2b Randomized, Double-Masked, Sham-Controlled, Study to Evaluate the Efficacy and Safety of Intravitreal Injection of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]. Clinical trial registration NCT04945772, clinicaltrials.gov, March 2024. submitted: 2021-06-15."},{"key":"2026041606200844000_2026.04.09.716230v1.10","unstructured":"Zhongmou Therapeutics. Prospective, Dose-Escalating, Investigator Initiated Trial to Evaluate the Safety and Efficacy of ZM-02 in Retinitis Pigmentosa. Clinical trial registration NCT06292650, clinicaltrials.gov, December 2024. submitted: 2024-02-27."},{"key":"2026041606200844000_2026.04.09.716230v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2018.09.003"},{"key":"2026041606200844000_2026.04.09.716230v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2011.155"},{"key":"2026041606200844000_2026.04.09.716230v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.12.117"},{"issue":"2","key":"2026041606200844000_2026.04.09.716230v1.14","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3390\/biomedicines13020429","article-title":"Evolution of Light-Sensitive Proteins in Optogenetic Approaches for Vision Restoration: A Comprehensive Review","volume":"13","year":"2025","journal-title":"Biomedicines"},{"key":"2026041606200844000_2026.04.09.716230v1.15","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1146\/annurev-vision-100119-124713","article-title":"Impact of Photoreceptor Loss on Retinal Circuitry","volume":"7","year":"2021","journal-title":"Annual Review of Vision Science"},{"issue":"1","key":"2026041606200844000_2026.04.09.716230v1.16","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-vision-110223-123044","article-title":"Impact of Glaucomatous Ganglion Cell Damage on Central Visual Function","volume":"10","year":"2024","journal-title":"Annual Review of Vision Science"},{"issue":"7","key":"2026041606200844000_2026.04.09.716230v1.17","first-page":"1774","article-title":"Scaling the Hill of Vision: The Physiological Relationship between Light Sensitivity and Ganglion Cell Numbers","volume":"41","year":"2000","journal-title":"Invest. 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