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This study focuses on developing a targeted approach by evaluating the efficacy of small peptides derived from pigment epithelium-derived factor (PEDF), known to restrict common cell death pathways associated with retinal diseases. Peptides with affinity for the PEDF receptor, PEDF-R, (17-mer and H105A) delivered via eye drops reached the retina, efficiently promoted photoreceptor survival, and improved retinal function in RP mouse models based on both the\n                  <jats:italic>rd10<\/jats:italic>\n                  mutation and the rhodopsin P23H mutation. Additionally, intravitreal delivery of AAV-H105A vectors delayed photoreceptor degeneration in the latter RP mouse model. Furthermore, peptide H105A specifically prevented photoreceptor death induced by oxidative stress, a contributing factor to RP progression, in human retinal organoids. This promising approach for peptide eye drop delivery holds significant potential as a therapeutic for preventing photoreceptor death in retinal disorders, offering a high safety profile, low invasiveness and multiple delivery options.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>Neurotrophic PEDF peptides delivered as eye drops preserve photoreceptor viability, morphology, and function in models of human retinal diseases.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.07.10.602890","type":"posted-content","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T19:00:12Z","timestamp":1721156412000},"source":"Crossref","is-referenced-by-count":2,"title":["H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0772-8225","authenticated-orcid":false,"given":"Alexandra","family":"Bernardo-Col\u00f3n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7584-1934","authenticated-orcid":false,"given":"Andrea","family":"Bighinati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8440-2055","authenticated-orcid":false,"given":"Shama","family":"Parween","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3858-8367","authenticated-orcid":false,"given":"Subrata","family":"Debnath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5073-7583","authenticated-orcid":false,"given":"Ilaria","family":"Piano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5294-0270","authenticated-orcid":false,"given":"Elisa","family":"Adani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9350-7948","authenticated-orcid":false,"given":"Francesca","family":"Corsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4992-9086","authenticated-orcid":false,"given":"Claudia","family":"Gargini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4545-8181","authenticated-orcid":false,"given":"Natalia","family":"Vergara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4428-2084","authenticated-orcid":false,"given":"Valeria","family":"Marigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8004-4983","authenticated-orcid":false,"given":"S. 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