RT Journal Article
T1 Systemic treatment with 7,8-Dihydroxiflavone activates TtkB and affords protection of two different retinal ganglion cell populations against axotomy in adult rats
A1 Vidal Villegas, Beatriz
A1 Pierdomenico, Johnny Di
A1 Gallego Ortega, Alejandro
A1 Galindo Romero, Caridad
A1 Martínez De La Casa Fernández-Borrella, José María
A1 García Feijoo, Julián
A1 Villegas Pérez, María Paz
A1 Vidal Sanz, Manuel
AB Purpose: 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.Methods: 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+RGCs and m+RGCs, respectively. Results: Optimal neuroprotection was achieved with 5 mg/kg DHF and resulted in TrkB phosphorylation. The percentage of surviving Brn3a+RGCs in vehicle treated rats was 60, 28, 18, 13, 12 or 8% of the original value at 7, 10, 14, 21, 30 or 60d, respectively, while in DHF treated retinas was 94, 70, 64, 17, 10 or 9% at the same time intervals. The percentages of m+RGCs diminished by 7d–13%, and recovered by 14d–38% in vehicle-treated and to 48% in DHF-treated retinas, without further variations. Conclusions: DHF neuroprotects Brn3a + RGCs and m + RGCs; its protective effects for Brn3a+RGCs are maximal at 7 days but still significant at 21d, whereas for m+RGCs neuroprotection was significant at 14d and permanent.
PB Elsevier
SN 0014-4835
YR 2021
FD 2021-07-08
LK https://hdl.handle.net/20.500.14352/4426
UL https://hdl.handle.net/20.500.14352/4426
LA eng
NO Vidal Villegas, B., Pierdomenico, J. D., Gallego Ortega, A. et al. «Systemic Treatment with 7,8-Dihydroxiflavone Activates TtkB and Affords Protection of Two Different Retinal Ganglion Cell Populations against Axotomy in Adult Rats». Experimental Eye Research, vol. 210, septiembre de 2021, p. 108694. DOI.org (Crossref), https://doi.org/10.1016/j.exer.2021.108694.
NO Fundación Séneca-Agencia de Ciencia y Tecnología de la Región de Murcia
NO Ministerio de Economía, Comercio y Empresa (España)
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Instituto de Salud Carlos III
NO Fondo Europeo de Desarrollo Regional
DS Docta Complutense
RD 19 dic 2025