7,8-Dihydroxiflavone Maintains Retinal Functionality and Protects Various Types of RGCs in Adult Rats with Optic Nerve Transection

To 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) (<i>n</i>...

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Autores principales:	Alejandro Gallego-Ortega, Beatriz Vidal-Villegas, María Norte-Muñoz, Manuel Salinas-Navarro, Marcelino Avilés-Trigueros, María Paz Villegas-Pérez, Manuel Vidal-Sanz
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	axotomy intraorbital optic nerve transection adult Sprague Dawley rat retinal ganglion cells 7,8-dihydroxiflavone full field electroretinogram Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/296fc6e874fa4151aa110d81782e8257
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spelling	oai:doaj.org-article:296fc6e874fa4151aa110d81782e82572021-11-11T17:15:23Z7,8-Dihydroxiflavone Maintains Retinal Functionality and Protects Various Types of RGCs in Adult Rats with Optic Nerve Transection10.3390/ijms2221118151422-00671661-6596https://doaj.org/article/296fc6e874fa4151aa110d81782e82572021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11815https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067To 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) (<i>n</i> = 24) and the other (<i>n</i> = 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 (<i>n</i> = 6). Treated rats were analyzed 7 (<i>n</i> = 14), 14 (<i>n</i> = 14) or 21 d (<i>n</i> = 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<sup>+</sup>), α-like (OPN<sup>+</sup>), α-OFF like (OPN<sup>+</sup>Brn3a<sup>+</sup>) or M4-like/α-ON sustained RGCs (OPN<sup>+</sup>Tbr<sup>+</sup>). 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<sup>+</sup>RGCs, OPN<sup>+</sup>RGCs and OPN<sup>+</sup>Tbr2<sup>+</sup>RGCs decreased to less than one half and OPN<sup>+</sup>Brn3a<sup>+</sup>RGCs decreased to approximately 0.5%, and Brn3a<sup>+</sup>RGCs showed a progressive loss with time, while OPN<sup>+</sup>RGCs and OPN<sup>+</sup>Tbr2<sup>+</sup>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<sup>+</sup>RGCs and OPN<sup>+</sup>Tbr2<sup>+</sup>RGCs for up to 14 d and of Brn3a<sup>+</sup>RGCs for up to 21 days. DHF affords significant rescue of Brn3a<sup>+</sup>RGCs, OPN<sup>+</sup>RGCs and OPN<sup>+</sup>Tbr2<sup>+</sup>RGCs, but not OPN<sup>+</sup>Brn3a<sup>+</sup>RGCs, and preserves functional ERG responses after IONT.Alejandro Gallego-OrtegaBeatriz Vidal-VillegasMaría Norte-MuñozManuel Salinas-NavarroMarcelino Avilés-TriguerosMaría Paz Villegas-PérezManuel Vidal-SanzMDPI AGarticleaxotomyintraorbital optic nerve transectionadult Sprague Dawley ratretinal ganglion cells7,8-dihydroxiflavonefull field electroretinogramBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11815, p 11815 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	axotomy intraorbital optic nerve transection adult Sprague Dawley rat retinal ganglion cells 7,8-dihydroxiflavone full field electroretinogram Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	axotomy intraorbital optic nerve transection adult Sprague Dawley rat retinal ganglion cells 7,8-dihydroxiflavone full field electroretinogram Biology (General) QH301-705.5 Chemistry QD1-999 Alejandro Gallego-Ortega Beatriz Vidal-Villegas María Norte-Muñoz Manuel Salinas-Navarro Marcelino Avilés-Trigueros María Paz Villegas-Pérez Manuel Vidal-Sanz 7,8-Dihydroxiflavone Maintains Retinal Functionality and Protects Various Types of RGCs in Adult Rats with Optic Nerve Transection
description	To 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) (<i>n</i> = 24) and the other (<i>n</i> = 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 (<i>n</i> = 6). Treated rats were analyzed 7 (<i>n</i> = 14), 14 (<i>n</i> = 14) or 21 d (<i>n</i> = 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<sup>+</sup>), α-like (OPN<sup>+</sup>), α-OFF like (OPN<sup>+</sup>Brn3a<sup>+</sup>) or M4-like/α-ON sustained RGCs (OPN<sup>+</sup>Tbr<sup>+</sup>). 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<sup>+</sup>RGCs, OPN<sup>+</sup>RGCs and OPN<sup>+</sup>Tbr2<sup>+</sup>RGCs decreased to less than one half and OPN<sup>+</sup>Brn3a<sup>+</sup>RGCs decreased to approximately 0.5%, and Brn3a<sup>+</sup>RGCs showed a progressive loss with time, while OPN<sup>+</sup>RGCs and OPN<sup>+</sup>Tbr2<sup>+</sup>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<sup>+</sup>RGCs and OPN<sup>+</sup>Tbr2<sup>+</sup>RGCs for up to 14 d and of Brn3a<sup>+</sup>RGCs for up to 21 days. DHF affords significant rescue of Brn3a<sup>+</sup>RGCs, OPN<sup>+</sup>RGCs and OPN<sup>+</sup>Tbr2<sup>+</sup>RGCs, but not OPN<sup>+</sup>Brn3a<sup>+</sup>RGCs, and preserves functional ERG responses after IONT.
format	article
author	Alejandro Gallego-Ortega Beatriz Vidal-Villegas María Norte-Muñoz Manuel Salinas-Navarro Marcelino Avilés-Trigueros María Paz Villegas-Pérez Manuel Vidal-Sanz
author_facet	Alejandro Gallego-Ortega Beatriz Vidal-Villegas María Norte-Muñoz Manuel Salinas-Navarro Marcelino Avilés-Trigueros María Paz Villegas-Pérez Manuel Vidal-Sanz
author_sort	Alejandro Gallego-Ortega
title	7,8-Dihydroxiflavone Maintains Retinal Functionality and Protects Various Types of RGCs in Adult Rats with Optic Nerve Transection
title_short	7,8-Dihydroxiflavone Maintains Retinal Functionality and Protects Various Types of RGCs in Adult Rats with Optic Nerve Transection
title_full	7,8-Dihydroxiflavone Maintains Retinal Functionality and Protects Various Types of RGCs in Adult Rats with Optic Nerve Transection
title_fullStr	7,8-Dihydroxiflavone Maintains Retinal Functionality and Protects Various Types of RGCs in Adult Rats with Optic Nerve Transection
title_full_unstemmed	7,8-Dihydroxiflavone Maintains Retinal Functionality and Protects Various Types of RGCs in Adult Rats with Optic Nerve Transection
title_sort	7,8-dihydroxiflavone maintains retinal functionality and protects various types of rgcs in adult rats with optic nerve transection
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/296fc6e874fa4151aa110d81782e8257
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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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