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We have previously shown that transplantation of human stem cell-derived cone photoreceptors (hCones) into young adult (3-month-old) mouse models of advanced retinal degeneration can restore retinal function. However, substantial remodeling of the remaining inner retinal circuitry continues long after complete photoreceptor loss, raising the critical question of whether photoreceptor transplantation can effectively rescue function at very late-stage degeneration. rd1 mice received transplants at 12-15\u2009months of age and were examined \u223c3\u2009months later. Transplanted hCones survived in large numbers, while host inner retinal neurons exhibited significant plasticity, extending dendrites to transplanted hCones, and making synapse-like contacts. Host M\u00fcller glia undergo notable remodeling, apparently incorporating the donor cells within the retinal structure. Multielectrode array recordings showed robust rescue of light-evoked activity across the normal photopic range intensities and evidence of inner retinal processing, while some treated mice showed improvements in visually evoked optokinetic head tracking behavior. Together, these data indicate that effective rescue following photoreceptor replacement therapy is feasible long after complete photoreceptor loss and extensive inner retinal remodeling.<\/jats:p>","DOI":"10.1093\/stmcls\/sxag023","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:37:19Z","timestamp":1777376239000},"source":"Crossref","is-referenced-by-count":5,"title":["Transplantation of human stem cell-derived cone photoreceptors partially restores vision in aged\n                    <i>rd1<\/i>\n                    mice with advanced retinal degeneration"],"prefix":"10.1093","volume":"44","author":[{"given":"Christopher A","family":"Procyk","sequence":"first","affiliation":[{"name":"Ocular Cell and Gene Therapy Group, King\u2019s College London Centre for Gene Therapy and Regenerative Medicine, Guy\u2019s Hospital , London, SE1 9RT,","place":["United 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