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7,8‐Dihydroxyflavone protects axotomy‐induced retinal ganglion cell loss in adult albino rats
Author(s) -
VidalVillegas Beatriz,
Di Pierdomenico Johnny,
SalinasNavarro Manuel,
Manuel BernalGarro Jose,
AgudoBarriuso Marta,
Paz VillegasPérez María,
Martínez de la Casa Jose M.,
GarcíaFeijoo Julián,
VidalSanz Manuel
Publication year - 2019
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2019.5413
Subject(s) - neuroprotection , axotomy , population , retinal ganglion cell , pharmacology , saline , retinal , biology , chemistry , medicine , endocrinology , central nervous system , biochemistry , environmental health
Purpose The substance 7,8‐dihydroxyflavone (DHF) is a potent agonist of the tropomyosin‐related kinase B (TrkB) receptor with a small molecular weight (254 Da) that crosses the blood brain barrier. We analyse the neuroprotective effects of systemically administered DHF on the survival of adult rat axotomized retinal ganglion cells (RGC) expressing Brn3a (Brn3a + RGCs). Methods In adult albino rats, the left optic nerve was intraorbitally transected (IONT). Rats were assigned to different groups that received daily intraperitoneal injections of saline (n=16) or DHF at different doses (1 mg/kg, n = 4; 2 mg/kg, n = 6; 4 mg/kg, n = 6; 5 mg/kg, n = 12; 10 mg/kg, n = 6; 25 mg/kg n = 6). Animals were analyzed 7 days after IONT, both retinas were dissected, prepared as wholemounts and immune‐labelled for Brn3a to identify surviving Brn3a + RGCs. Total numbers of surviving Brn3a + RGCs were quantified automatically and their topographical distribution was examined with the construction of isodensity maps. Results Seven days after IONT, treatment with saline alone or with low doses of DHF (1mg/kg, 2mg/kg) results in the loss of approximately 40% of the RGC population, whereas treatment with medium doses of DHF (4 or 5mg/kg) resulted in significant neuroprotection with loss of only 15% or 7% of the RGC population, and treatment with high doses of DHF (10 or 25mg/kg) caused loss of 26 or 29% of the RGC population. Conclusion Our data show that DHF has significant RGC neuroprotective effects, and that the most effective doses are 4‐5mg/kg.