{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:10:51Z","timestamp":1788948651365,"version":"build-2803163510"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sci.","Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Optic nerve injury involves heterogeneous neuronal and microenvironmental responses that may require sequential, state-dependent intervention. BioEdge-RGC was developed as a transcriptomics-informed computational benchmark for transferring a globally planned model-predictive-control policy to compact regional neural models operating with incomplete observations and reduced communication. Methods: Public mouse optic-nerve-crush transcriptomic datasets were summarized into seven retinal ganglion cell modules and eight retinal environment modules and fused into a 15-dimensional temporal reference state for a 16-region, five-step simulator. A candidate-constrained MPC expert was approximated by a central neural teacher and local, neighbour-aware, and coordinated regional students trained using hybrid knowledge distillation or direct MPC supervision. Missing observations, severe simulated injury, INT8 quantization, local parameter perturbations, and an independent GSE229033 transcriptomic plausibility assessment were evaluated. Results: The central teacher retained 99.90% of the MPC objective, and the coordinated distilled student retained 99.69% of teacher performance while reducing modeled communication from 5520 to 1080 bytes per episode. The coordinated-versus-local mean-objective difference was +0.000053 and did not meet the predefined +0.008 threshold; direct MPC supervision performed at least as well as hybrid distillation. The principal objective-based conclusions were preserved across all nine local parameter conditions, whereas the coordinated failure-rate advantage was not parameter-robust. In GSE229033, six of seven modules changed in the predefined favorable direction, but the oriented composite bootstrap interval included zero. Conclusions: Compact regional neural policies reproduced MPC performance with minimal objective loss and substantially lower modeled communication. The external transcriptomic analysis provided limited plausibility support for the RGC state orientation, while neither analysis validated simulator dynamics, controller efficacy, biological treatment effects, or clinical applicability.<\/jats:p>","DOI":"10.3390\/brainsci16090941","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:35:29Z","timestamp":1788359729000},"page":"941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BioEdge-RGC: Compact Neural Policy Transfer from Model-Predictive Control in a Transcriptomics-Informed Optic Nerve Injury Simulation"],"prefix":"10.3390","volume":"16","author":[{"given":"Roxana Irina","family":"Iancu","sequence":"first","affiliation":[{"name":"Department of Oral Pathology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"},{"name":"Department of Oncology and Radiotherapy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"},{"name":"Department of Clinical Laboratory, \u201cSf\u00e2ntul Spiridon\u201d Emergency Hospital, 700111 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucian","family":"Eva","sequence":"additional","affiliation":[{"name":"\u201cProf. Dr. Nicolae Oblu\u201d Clinical Emergency Hospital, 700309 Ia\u0219i, Romania"},{"name":"Faculty of Medicine and Pharmacy, \u201cDun\u0103rea de Jos\u201d University of Gala\u021bi, 800008 Gala\u021bi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2791-3400","authenticated-orcid":false,"given":"C\u0103lin Gheorghe","family":"Buzea","sequence":"additional","affiliation":[{"name":"\u201cProf. Dr. Nicolae Oblu\u201d Clinical Emergency Hospital, 700309 Ia\u0219i, Romania"},{"name":"National Institute of Research and Development for Technical Physics\u2014IFT Iasi, 700050 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3863-6904","authenticated-orcid":false,"given":"Florin","family":"Nedeff","sequence":"additional","affiliation":[{"name":"Department of Environmental Engineering, Mechanical Engineering and Agritourism, Faculty of Engineering, \u201cVasile Alecsandri\u201d University of Bac\u0103u, 600115 Bac\u0103u, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Nedeff","sequence":"additional","affiliation":[{"name":"Department of Environmental Engineering, Mechanical Engineering and Agritourism, Faculty of Engineering, \u201cVasile Alecsandri\u201d University of Bac\u0103u, 600115 Bac\u0103u, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0922-740X","authenticated-orcid":false,"given":"Diana","family":"Miril\u0103","sequence":"additional","affiliation":[{"name":"Department of Environmental Engineering, Mechanical Engineering and Agritourism, Faculty of Engineering, \u201cVasile Alecsandri\u201d University of Bac\u0103u, 600115 Bac\u0103u, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8582-1988","authenticated-orcid":false,"given":"Mirela","family":"Panainte-Lehadu\u0219","sequence":"additional","affiliation":[{"name":"Department of Environmental Engineering, Mechanical Engineering and Agritourism, Faculty of Engineering, \u201cVasile Alecsandri\u201d University of Bac\u0103u, 600115 Bac\u0103u, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maricel","family":"Agop","sequence":"additional","affiliation":[{"name":"Department of Environmental Engineering, Mechanical Engineering and Agritourism, Faculty of Engineering, \u201cVasile Alecsandri\u201d University of Bac\u0103u, 600115 Bac\u0103u, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Irina","family":"Gr\u0103dinaru","sequence":"additional","affiliation":[{"name":"Department of Implantology, Removable Dentures, Technology, Discipline of Dental Materials, Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Drago\u0219 Petru Teodor","family":"Iancu","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"},{"name":"Department of Oncology and Radiotherapy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"},{"name":"\u201cProf. Dr. Nicolae Oblu\u201d Clinical Emergency Hospital, 700309 Ia\u0219i, Romania"},{"name":"Department of Radiotherapy, Regional Institute of Oncology, 700483 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.neuron.2019.11.006","article-title":"Single-cell profiles of retinal ganglion cells differing in resilience to injury reveal neuroprotective genes","volume":"104","author":"Tran","year":"2019","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1126\/science.1161566","article-title":"Promoting axon regeneration in the adult CNS by modulation of the PTEN\/mTOR pathway","volume":"322","author":"Park","year":"2008","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nature10594","article-title":"Sustained axon regeneration induced by co-deletion of PTEN and SOCS3","volume":"480","author":"Sun","year":"2011","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.tips.2024.11.008","article-title":"Emerging therapeutic strategies for optic nerve regeneration","volume":"46","author":"Zhang","year":"2025","journal-title":"Trends Pharmacol. 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Rep."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/9\/941\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:56:35Z","timestamp":1788947795000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/9\/941"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,2]]},"references-count":27,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["brainsci16090941"],"URL":"https:\/\/doi.org\/10.3390\/brainsci16090941","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,2]]}}}