7,8-Dihydroxyflavone protects axotomy-induced retinal ganglion cell loss in adult albino rats.

Abstract

Purpose : To investigate the long-term neuroprotective effects of 7,8-dihydroxyflavone (DHF), a potent agonist of the tropomyosin-related kinase B (TrkB) receptor with a small molecular weight (254 Da) that crosses the blood brain barrier, against axotomy-induced RGC loss.

Methods : In adult albino Sprague-Dawley rats, the left optic nerve was intraorbitally transected (IONT). Because previous studies from our group have shown that DHF administered systemically provided maximum protection at a dose of 5mg/kg, in the present studies Rats were assigned to different groups that received daily intraperitoneal injections of saline or DHF (5 mg/kg) and were analyzed 7 (n=13), 10 (n=13), 14 (n=13), 21 (n=14), 30 (n=14) or 60 (n=14) days rafter 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 : The mean total number of Brn3a⁺RGCs in the right eyes was 81,304±1680 (mean±SD; n=80) and served as control. Treatment with Saline resulted in the loss of approximately 41%, 72%, 82%, 86%, 89% or 91% of the original RGC population at 7(n=6), 10(n=6), 14(n=6), 21(n=6), 30(n=6) or 60(n=6) days, respectively, whereas treatment with DHF resulted in significant neuroprotection that was maintained up to 21 days after IONT. The proportion of surviving Brn3a⁺RGCs in the DHF treated groups were approximately 92%, 71%, 64%, 17%, 10% or 9% of the original RGC population at 7(n=7), 10(n=7), 14(n=7), 21(n=8), 30(n=8) or 60(n=8) days, respectively.

Conclusions : DHF affords significant neuroprotection against axotomy-induced RGC loss that lasts up to 21 days after IONT.

This is a 2020 ARVO Annual Meeting abstract.