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Despite the causative genetic mutation typically not expressed in cone photoreceptors, these cells inevitably degenerate following the primary death of rods, causing blindness. The reasons for the \u201cbystander\u201d degeneration of cones are presently unknown but decrement of survival factors, oxidative stress, and inflammation all play a role. Targeting these generalized biological processes represents a strategy to develop mutation-agnostic therapies for saving vision in large populations of RP individuals. A classical method to support neuronal survival is by employing neurotrophic factors, such as NGF. This study uses painless human NGF (hNGFp), a TrkA receptor-biased variant of the native molecule with lower affinity for nociceptors and limited activity as a pain inducer; the molecule has identical neurotrophic power of the native form but a reduced affinity for the p75NTR receptors, known to trigger apoptosis. hNGFp has a recognized activity on brain microglial cells, which are induced to a phenotype switch from a highly activated to a more homeostatic configuration. hNGFp was administered to RP-like mice in vivo with the aim of decreasing retinal inflammation and also providing retinal neuroprotection. However, the ability of this treatment to counteract the bystander degeneration of cones remained limited.<\/jats:p>","DOI":"10.1523\/eneuro.0096-24.2024","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T17:50:19Z","timestamp":1726681819000},"page":"ENEURO.0096-24.2024","source":"Crossref","is-referenced-by-count":5,"title":["Human NGF \u201cPainless\u201d Ocular Delivery for Retinitis Pigmentosa: An In Vivo Study"],"prefix":"10.1523","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1002-4244","authenticated-orcid":false,"given":"Debora","family":"Napoli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noemi","family":"Orsini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Salamone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria 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