TY - JOUR T1 - Systemic treatment with 7,8-Dihydroxiflavone activates TtkB and affords protection of two different retinal ganglion cell populations against axotomy in adult rats. AU - Vidal-Villegas,Beatriz, AU - Di Pierdomenico,Johnny, AU - Gallego-Ortega,Alejandro, AU - Galindo-Romero,Caridad, AU - Martínez-de-la-Casa,Jose M, AU - García-Feijoo,Julian, AU - Villegas-Pérez,María P, AU - Vidal-Sanz,Manuel, Y1 - 2021/07/08/ PY - 2021/04/01/received PY - 2021/05/26/revised PY - 2021/07/01/accepted PY - 2021/7/11/pubmed PY - 2021/10/9/medline PY - 2021/7/10/entrez KW - 7,8-Dihydroxiflavone KW - Adult albino rats KW - Apoptosis KW - Axotomy KW - BDNF neuroprotection KW - BDNF-Mimetic KW - Brn3a KW - Intraorbital optic nerve transection KW - Intrinsically photosensitive retinal ganglion cells KW - Melanopsin KW - Neuroprotection KW - Optic nerve section KW - Retinal ganglion cells SP - 108694 EP - 108694 JF - Experimental eye research JO - Exp Eye Res VL - 210 N2 - 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. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/34245756/Systemic_treatment_with_78_Dihydroxiflavone_activates_TtkB_and_affords_protection_of_two_different_retinal_ganglion_cell_populations_against_axotomy_in_adult_rats_ DB - PRIME DP - Unbound Medicine ER -