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7,8-Dihydroxiflavone maintains retinal functionality and protects various types of RGCs in adult rats with optic nerve transection

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dc.contributor.authorGallego Ortega, Alejandro
dc.contributor.authorVidal Villegas, Beatriz
dc.contributor.authorNorte Muñoz, María
dc.contributor.authorSalinas Navarro, Manuel Ángel
dc.contributor.authorAvilés Trigueros, Marcelino
dc.contributor.authorVillegas Pérez, Maria Paz
dc.contributor.authorVidal Sanz, Manuel
dc.contributor.departmentOftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
dc.contributor.otherFacultades de la UMU::Facultad de Medicina
dc.date.accessioned2026-01-27T11:45:24Z
dc.date.available2026-01-27T11:45:24Z
dc.date.copyright© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
dc.date.copyright© 2021 by the authors
dc.date.issued2021-10-30
dc.description.abstractTo analyze the neuroprotective effects of 7,8-Dihydroxyflavone (DHF) in vivo and ex vivo, adult albino Sprague-Dawley rats were given a left intraorbital optic nerve transection (IONT) and were divided in two groups: One was treated daily with intraperitoneal (ip) DHF (5 mg/kg) (n = 24) and the other (n = 18) received ip vehicle (1% DMSO in 0.9% NaCl) from one day before IONT until processing. At 5, 7, 10, 12, 14, and 21 days (d) after IONT, full field electroretinograms (ERG) were recorded from both experimental and one additional naïve-control group (n = 6). Treated rats were analyzed 7 (n = 14), 14 (n = 14) or 21 d (n = 14) after IONT, and the retinas immune stained against Brn3a, Osteopontin (OPN) and the T-box transcription factor T-brain 2 (Tbr2) to identify surviving retinal ganglion cells (RGCs) (Brn3a+), α-like (OPN+), α-OFF like (OPN+Brn3a+) or M4-like/α-ON sustained RGCs (OPN+Tbr+). Naïve and right treated retinas showed normal ERG recordings. Left vehicle-treated retinas showed decreased amplitudes of the scotopic threshold response (pSTR) (as early as 5 d), the rod b-wave, the mixed response and the cone response (as early as 10 d), which did not recover with time. In these retinas, by day 7 the total numbers of Brn3a+RGCs, OPN+RGCs and OPN+Tbr2+RGCs decreased to less than one half and OPN+Brn3a+RGCs decreased to approximately 0.5%, and Brn3a+RGCs showed a progressive loss with time, while OPN+RGCs and OPN+Tbr2+RGCs did not diminish after seven days. Compared to vehicle-treated, the left DHF-treated retinas showed significantly greater amplitudes of the pSTR, normal b-wave values and significantly greater numbers of OPN+RGCs and OPN+Tbr2+RGCs for up to 14 d and of Brn3a+RGCs for up to 21 days. DHF affords significant rescue of Brn3a+RGCs, OPN+RGCs and OPN+Tbr2+RGCs, but not OPN+Brn3a+RGCs, and preserves functional ERG responses after IONT.
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dc.format.extent27
dc.identifier.citationInt J Mol Sci. 2021 Oct 30;22(21):11815. doi: 10.3390/ijms222111815
dc.identifier.doihttps://doi.org/10.3390/ijms222111815
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttp://hdl.handle.net/10201/194749
dc.languageeng
dc.publisherMDPI
dc.relationFundación Séneca, Agencia de Ciencia y Tecnología Región de Murcia: 19881/GERM/15 to M. V.-S.; Instituto de Salud Carlos III: PI19/00203 and RD16/0008/0026, both cofinanced by ERDF “A way of making Europe” to M.P. V.-P.; RED2018-102499-T and PID2019-106498GB-I00 funded by MCIN/AEI/ 10.13039/501100011033 to M. V.-S. and M.V.-S. and M. A.-T., respectively.
dc.relation.publisherversionhttps://www.mdpi.com/1422-0067/22/21/11815
dc.rightsAttribution 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject7,8-dihydroxiflavone; Brn3a; M4 ipRGC/α-ON-Sustained RGC; Tbr2 (T-box transcription factor T-brain 2); adult Sprague Dawley rat; axotomy; full field electroretinogram; intraorbital optic nerve transection; osteopontin (OPN); retinal ganglion cells; scotopic threshold response (STR); α-OFF RGCs; α-RGCs.
dc.subjectAaxotomy
dc.subjectIntraorbital optic nerve transection
dc.subjectAdult Sprague Dawley rat
dc.subjectRetinal ganglion cells
dc.subject7,8 dihydroxiflavone
dc.subjectFull field electroretinogram
dc.subjectScotopic threshold response STR
dc.subjectBrn3a
dc.subjectOsteopontin OPN
dc.subjectTbr2
dc.subjectT box transcription factor T brain 2
dc.subjectα-RGCs
dc.subjectα-OFF RGCs
dc.subjectM4 ipRGC/α-ON-Sustained RGC
dc.subject.odsObjetivo 3: Salud
dc.title7,8-Dihydroxiflavone maintains retinal functionality and protects various types of RGCs in adult rats with optic nerve transection
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
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