Vidal Villegas, BeatrizPierdomenico, Johnny DiGallego Ortega, AlejandroGalindo Romero, CaridadMartínez De La Casa Fernández-Borrella, José MaríaGarcía Feijoo, JuliánVillegas Pérez, María PazVidal Sanz, Manuel2023-06-162023-06-162021-07-08Vidal 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.2021.108694.0014-483510.1016/j.exer.2021.108694https://hdl.handle.net/20.500.14352/4426Purpose: 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.engjournal articlehttps://doi.org/10.1016/j.exer.2021.108694http://www.journals.elsevier.com/experimental-eye-research/restricted access617.73547.96616‑092.9616.8-003.8Optic nerve sectionAxotomyIntraorbital optic nerve transectionIntrinsically photosensitive retinal ganglionCellsBDNF neuroprotection78-DihydroxiflavoneMelanopsinRetinal ganglion cellsApoptosisAdult albino ratsBrn3aNeuroprotectionBDNF-MimeticNeurociencias (Medicina)Oftalmología2490 Neurociencias3201.09 Oftalmología