{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:54:36Z","timestamp":1785430476169,"version":"3.56.0"},"posted":{"date-parts":[[2026,1,12]]},"group-title":"Genetics","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01EY032666"],"award-info":[{"award-number":["R01EY032666"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01EY033015"],"award-info":[{"award-number":["R01EY033015"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RO1EY027004"],"award-info":[{"award-number":["RO1EY027004"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RO1EY033010"],"award-info":[{"award-number":["RO1EY033010"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30 EY002162"],"award-info":[{"award-number":["P30 EY002162"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]},{"award":["ZIAEY000450 and ZIAEY000546. (Intramural Research Program NEI)"],"award-info":[{"award-number":["ZIAEY000450 and ZIAEY000546. (Intramural Research Program NEI)"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/04drjs621","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Myopia is a leading cause of visual impairment worldwide, and high myopia markedly increases the risk of irreversible vision loss. Although visual experience guides postnatal ocular elongation, the role of intrinsic retinal growth signals remains poorly defined. Here we identify the serine protease PRSS56 as a retinal factor that promotes ocular axial growth beyond early development. Using genetic mouse models, we show that conditional inactivation of Prss56 in M\u00fcller glia reduces axial length and causes hyperopia even under dark-rearing conditions, demonstrating that PRSS56 drives axial elongation independently of light-evoked visual input during emmetropization. Conversely, M\u00fcller glia-specific overexpression of Prss56 induces axial elongation in a proteolysis-dependent manner, supporting its role as an autonomous retinal growth signal. In concordance, human genetic analyses reveal that the common\n                  <jats:italic>PRSS56<\/jats:italic>\n                  variant rs2853447 is associated with increased axial length in individuals with myopia and high myopia, but not in non-myopes, suggesting that this variant confers a selective growth advantage in individuals predisposed to ocular elongation. Functional genomic analyses further identify a myopia-associated variant, rs2741297, within a retinal enhancer in intron 4 of\n                  <jats:italic>PRSS56<\/jats:italic>\n                  marked by open chromatin and transcription factor occupancy. Together, these findings establish PRSS56 as an intrinsic retinal growth factor that functions beyond early eye development and support a model in which genetic and environmental factors converge on retinal pathways to modulate myopia susceptibility.\n                <\/jats:p>","DOI":"10.64898\/2026.01.11.697334","type":"posted-content","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T02:15:17Z","timestamp":1768270517000},"source":"Crossref","is-referenced-by-count":0,"title":["PRSS56 acts as an intrinsic retinal signal driving postnatal ocular axial growth and myopia susceptibility"],"prefix":"10.64898","author":[{"given":"Kiran","family":"Gangappa","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Durairaj","family":"Duraikannu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayshree","family":"Advani","sequence":"additional","affiliation":[{"name":"Neurobiology, Neurodegeneration, & Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandre","family":"Labelle-Dumais","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emre Berk","family":"Uludag","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nivedita","family":"Singh","sequence":"additional","affiliation":[{"name":"Neurobiology, Neurodegeneration, & Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swanand","family":"Koli","sequence":"additional","affiliation":[{"name":"Grousbeck Gene Therapy Center, Schepens Eye Research Institute, and Massachusetts Eye and Ear Infirmary, Boston, MA, USA"},{"name":"Department of Ophthalmology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Kaiser Permanente, Division of Research, Pleasanton, CA 94588, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yien-Ming","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Choquet","sequence":"additional","affiliation":[{"name":"Kaiser Permanente, Division of Research, Pleasanton, CA 94588, USA"},{"name":"Department of Health Systems Science Kaiser Permanente Bernard J. 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