Effects of age on chick light adapted ERGs with and without inner retinal excitotoxic damage

Abstract

Purpose : N-methyl-D-aspartate (NMDA) retinal damage model is commonly used in the chick to model human disorders such as glaucoma, retinal ischemia, vascular occlusion, diabetic retinopathy, and blast injury. Little is known about the impact of NMDA excitotoxic damage on retinal function. We analyzed the impact of age (up to post hatch day 35 (P35)) on retinal function in chicks with and without NMDA inner retina excitotoxic damage.

Methods : IACUC approval was obtained. We evaluated untreated male leghorn chicks (n=3/group) with weekly ERG (UTAS 3000) under isoflurane anesthesia at P14 through P35. We evaluated chicks treated with intravitreal NMDA (500nmol/20μL) injection in the left eye and vehicle in the right eye at P14. ERGs were performed on each eye at day 1 (D1), D7, and D14 post-injection as well as on untreated age-matched controls. Chick temperature was monitored and maintained. The light adapted ERG, the light adapted flicker, and long flash ERG (ON/OFF) were performed first on the left eye then on the right eye. Amplitudes and peak times of the a-, b-, d-waves, sum of the oscillatory potentials (SOP) and flicker ERG were calculated.

Results : We found that untreated subjects had decreased amplitudes of almost all measured parameters with increasing age (e.g., P14 vs. P35: a- (180±33µV vs. 119±18µV), b-wave (525±64µV vs. 359±33µV); p < 0.0001). We observed that NMDA treatment significantly reduced the amplitude of all measured parameters at D1 (e.g., NMDA vs. Saline: a- (90±27µV vs. 162±22µV), b-wave (127±16µV vs. 335±46µV); p ≤ 0.0001). The a-wave peak times for NMDA D1 treatment showed a significant delay in the response (NMDA vs Saline: (14±3ms vs. 10±0.6ms) p = 0.0039). All metrics improved over time, with only the b-wave remaining significantly different from controls at D14 (NMDA vs. Saline: (238±20µV vs. 319±69µV) p = 0.0230).

Conclusions : In normal chicks, the light adapted ERG amplitudes decrease over a period of three weeks. Peak times remain unchanged. NMDA retinal damage shows an initial impact on both inner (b-wave) and outer (a-wave) retinal light responses (amplitudes and peak times) with some recovery over time. Future studies will evaluate the impact of neuroprotective agents on these responses.

This is a 2020 ARVO Annual Meeting abstract.