{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T20:20:01Z","timestamp":1773519601595,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,12]]},"group-title":"Neuroscience","reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["R01EY032542"],"award-info":[{"award-number":["R01EY032542"]}]},{"name":"NIH","award":["R01EY034531"],"award-info":[{"award-number":["R01EY034531"]}]},{"name":"NIH","award":["P30EY030413"],"award-info":[{"award-number":["P30EY030413"]}]},{"name":"The Fichtenbaum Charitable Trust Research Award"},{"name":"Anne Marie & Thomas B. Walker Fund"},{"name":"Challenge Grant from Research to Prevent Blindness"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>To characterize the cellular tropism and temporal dynamics of adeno-associated virus 2 (AAV2)-retro\u2013mediated gene delivery in the adult mouse retina following intravitreal injection.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Adult C57BL\/6J mice received single or sequential intravitreal injections of AAV2-retro carrying the mGreenLantern (mGL) reporter gene. Retinas were collected at 1-, 3-, and 14-days post-injection (dpi) and processed for immunofluorescence analysis. Transduced cell types were identified using cell-type markers, including cone arrestin, RBPMS, and AP-2\u03b1. The number and distribution of mGL-positive cells were quantified on whole retinas or retinal cross-sections to assess transduction efficiency, specificity, and spatial coverage.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Reporter expression was detected in the outer retina at 1 dpi and increased markedly at 3 and 14 dpi. AAV2-retro demonstrated strong tropism for photoreceptors and retinal pigment epithelium (RPE), with robust labeling of both rods and cones. In contrast to the robust outer retinal expression, transduction in the inner nuclear layers was limited to a few retinal ganglion and amacrine cells, reflecting strong cell-type specificity. Reporter expression was distributed widely across the retina, exceeding the localized pattern typically observed following subretinal delivery with conventional AAV2 vectors. Sequential injections further increased reporter expression and spatial coverage compared with single injections.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>AAV2-retro enables efficient, outer retina\u2013specific gene delivery following intravitreal administration. This approach overcomes the limitations of traditional intravitreal gene transfer and provides a minimally invasive alternative to subretinal injection. AAV2-retro\u2013 mediated transduction may facilitate preclinical studies of retinal degeneration and support the development of gene therapies aimed at preserving photoreceptors and RPE function.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.10.710806","type":"posted-content","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:20:23Z","timestamp":1773361223000},"source":"Crossref","is-referenced-by-count":0,"title":["AAV2-Retro-Mediated Gene Transfer Selectively Targets Outer Retinal Cells Following Intravitreal Injection"],"prefix":"10.64898","author":[{"given":"Chaimaa","family":"Kinane","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Texas Southwestern Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moxa","family":"Panchal","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Texas Southwestern Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pantelis","family":"Tsoulfas","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venu","family":"Talla","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Texas Southwestern Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4796-3894","authenticated-orcid":false,"given":"Kevin K.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Texas Southwestern Medical Center"},{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center"},{"name":"Peter O\u2019Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026031409300424000_2026.03.10.710806v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2023.08.044"},{"key":"2026031409300424000_2026.03.10.710806v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2022.108961"},{"key":"2026031409300424000_2026.03.10.710806v1.3","doi-asserted-by":"publisher","DOI":"10.3390\/cells14010049"},{"key":"2026031409300424000_2026.03.10.710806v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31868-8"},{"key":"2026031409300424000_2026.03.10.710806v1.5","doi-asserted-by":"publisher","DOI":"10.21037\/atm-20-4726"},{"key":"2026031409300424000_2026.03.10.710806v1.6","doi-asserted-by":"publisher","DOI":"10.1177\/10430342251379824"},{"key":"2026031409300424000_2026.03.10.710806v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-0016(03)00144-8"},{"issue":"97","key":"2026031409300424000_2026.03.10.710806v1.8","first-page":"67","article-title":"State-of-the-art human gene therapy: part I","volume":"18","year":"2014","journal-title":"Gene delivery technologies. 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