{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T22:37:22Z","timestamp":1776465442884,"version":"3.51.2"},"reference-count":35,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,3]],"date-time":"2021-10-03T00:00:00Z","timestamp":1633219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Saffron treatment and photobiomodulation (PBM) are non-invasive therapeutic approaches able to mitigate and stabilize retinal degenerative diseases such as age-related macular degeneration (AMD). Although different, these therapies partially match their modulated pattern of genes. Recent attempts to find an additive effect by coadministration of saffron and PBM have failed. Instead, in this study, a different protocol to increase neuroprotection by providing consecutive saffron and PBM treatment administration is suggested. Materials and Methods: Albino rats, whose retinal damage was caused by light exposure (LD, light damage), were subjected to differential treatment protocols before and after LD: (1) PBM followed by saffron; and (2) single treatments of PBM. Thinning of the photoreceptor layer and neuro-inflammatory markers for gliosis and microglia were assessed via immune-histochemical techniques. Results: Results confirm that PBM and saffron alone cope with retinal neurodegenerative processes, preserving retinal thickness and gliosis and microglia invasion in a differential way. However, the synergistic effect of the combined treatment was restricted to the early neuroinflammation, even when provided sequentially. Conclusion: The broad spectra of action of both neuroprotectants require further investigation to identify other key pathways helpful in enhancing the effects of these two approaches in combination.<\/jats:p>","DOI":"10.3390\/medicina57101059","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T01:57:54Z","timestamp":1633917474000},"page":"1059","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sequential PBM\u2013Saffron Treatment in an Animal Model of Retinal Degeneration"],"prefix":"10.3390","volume":"57","author":[{"given":"Mattia","family":"Di Paolo","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno, 6, 56121 Pisa, Italy"},{"name":"Interuniversity Consortium Biostructures and Biosystems National Institute, Via Medaglie d\u2019Oro 305, 00136 Roma, Italy"},{"name":"Department of Biotechnological and Applied Clinical Sciences, University of l\u2019Aquila, Via Vetoio, 1, 67100 l\u2019Aquila, Italy"},{"name":"Bio Aurum srl, Via Mangionello, 12, 73024 Maglie, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100825","DOI":"10.1016\/j.preteyeres.2019.100825","article-title":"Age-related macular degeneration: A two-level model hypothesis","volume":"76","author":"Rozing","year":"2020","journal-title":"Prog. 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