Systemic treatment with 7,8-Dihydroxiflavone activates TtkB and affords protection of two different retinal ganglion cell populations against axotomy in adult rats.


Journal

Experimental eye research
ISSN: 1096-0007
Titre abrégé: Exp Eye Res
Pays: England
ID NLM: 0370707

Informations de publication

Date de publication:
09 2021
Historique:
received: 01 04 2021
revised: 26 05 2021
accepted: 01 07 2021
pubmed: 11 7 2021
medline: 9 10 2021
entrez: 10 7 2021
Statut: ppublish

Résumé

To analyze responses of different RGC populations to left intraorbital optic nerve transection (IONT) and intraperitoneal (i.p.) treatment with 7,8-Dihydroxyflavone (DHF), a potent selective TrkB agonist. Adult albino Sprague-Dawley rats received, following IONT, daily i.p. injections of vehicle (1%DMSO in 0.9%NaCl) or DHF. Group-1 (n = 58) assessed at 7days (d) the optimal DHF amount (1-25 mg/kg). Group-2, using freshly dissected naïve or treated retinas (n = 28), investigated if DHF treatment was associated with TrkB activation using Western-blotting at 1, 3 or 7d. Group-3 (n = 98) explored persistence of protection and was analyzed at survival intervals from 7 to 60d after IONT. Groups 2-3 received daily i.p. vehicle or DHF (5 mg/kg). Retinal wholemounts were immunolabelled for Brn3a and melanopsin to identify Brn3a Optimal neuroprotection was achieved with 5 mg/kg DHF and resulted in TrkB phosphorylation. The percentage of surviving Brn3a DHF neuroprotects Brn3a 

Identifiants

pubmed: 34245756
pii: S0014-4835(21)00260-8
doi: 10.1016/j.exer.2021.108694
pii:
doi:

Substances chimiques

6,7-dihydroxyflavone 0
Flavones 0
Neuroprotective Agents 0
Rod Opsins 0
Transcription Factor Brn-3A 0
melanopsin 0
Ntrk2 protein, rat EC 2.7.10.1
Receptor, trkB EC 2.7.10.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

108694

Informations de copyright

Copyright © 2021. Published by Elsevier Ltd.

Auteurs

Beatriz Vidal-Villegas (B)

Servicio de Oftalmología, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain; Departamento de Oftalmología, Universidad de Murcia e Instituto Murciano de Investigación Biosanitaria (IMIB) Virgen de la Arrixaca. Campus de CC de la Salud, 30120, El Palmar, Murcia, Spain.

Johnny Di Pierdomenico (J)

Departamento de Oftalmología, Universidad de Murcia e Instituto Murciano de Investigación Biosanitaria (IMIB) Virgen de la Arrixaca. Campus de CC de la Salud, 30120, El Palmar, Murcia, Spain.

Alejandro Gallego-Ortega (A)

Departamento de Oftalmología, Universidad de Murcia e Instituto Murciano de Investigación Biosanitaria (IMIB) Virgen de la Arrixaca. Campus de CC de la Salud, 30120, El Palmar, Murcia, Spain.

Caridad Galindo-Romero (C)

Departamento de Oftalmología, Universidad de Murcia e Instituto Murciano de Investigación Biosanitaria (IMIB) Virgen de la Arrixaca. Campus de CC de la Salud, 30120, El Palmar, Murcia, Spain.

Jose M Martínez-de-la-Casa (JM)

Servicio de Oftalmología, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain.

Julian García-Feijoo (J)

Servicio de Oftalmología, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain.

María P Villegas-Pérez (MP)

Servicio de Oftalmología, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain; Departamento de Oftalmología, Universidad de Murcia e Instituto Murciano de Investigación Biosanitaria (IMIB) Virgen de la Arrixaca. Campus de CC de la Salud, 30120, El Palmar, Murcia, Spain.

Manuel Vidal-Sanz (M)

Departamento de Oftalmología, Universidad de Murcia e Instituto Murciano de Investigación Biosanitaria (IMIB) Virgen de la Arrixaca. Campus de CC de la Salud, 30120, El Palmar, Murcia, Spain. Electronic address: manuel.vidal@um.es.

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Classifications MeSH