7,8-Dihydroxiflavone Maintains Retinal Functionality and Protects Various Types of RGCs in Adult Rats with Optic Nerve Transection.

To analyze the neuroprotective effects of 7,8-Dihydroxyflavone (DHF) in vivo and ex vivo, adult albino Sprague-Dawley rats were given a left intraorbital optic nerve transection (IONT) and were divided in two groups: One was treated daily with intraperitoneal (ip) DHF (5 mg/kg) ( = 24) and the other ( = 18) received ip vehicle (1% DMSO in 0.9% NaCl) from one day before IONT until processing. At 5, 7, 10, 12, 14, and 21 days (d) after IONT, full field electroretinograms (ERG) were recorded from both experimental and one additional naïve-control group ( = 6). Treated rats were analyzed 7 ( = 14), 14 ( = 14) or 21 d ( = 14) after IONT, and the retinas immune stained against Brn3a, Osteopontin (OPN) and the T-box transcription factor T-brain 2 (Tbr2) to identify surviving retinal ganglion cells (RGCs) (Brn3a), α-like (OPN), α-OFF like (OPNBrn3a) or M4-like/α-ON sustained RGCs (OPNTbr). Naïve and right treated retinas showed normal ERG recordings. Left vehicle-treated retinas showed decreased amplitudes of the scotopic threshold response (pSTR) (as early as 5 d), the rod b-wave, the mixed response and the cone response (as early as 10 d), which did not recover with time. In these retinas, by day 7 the total numbers of Brn3aRGCs, OPNRGCs and OPNTbr2RGCs decreased to less than one half and OPNBrn3aRGCs decreased to approximately 0.5%, and Brn3aRGCs showed a progressive loss with time, while OPNRGCs and OPNTbr2RGCs did not diminish after seven days. Compared to vehicle-treated, the left DHF-treated retinas showed significantly greater amplitudes of the pSTR, normal b-wave values and significantly greater numbers of OPNRGCs and OPNTbr2RGCs for up to 14 d and of Brn3aRGCs for up to 21 days. DHF affords significant rescue of Brn3aRGCs, OPNRGCs and OPNTbr2RGCs, but not OPNBrn3aRGCs, and preserves functional ERG responses after IONT.