Effect of NMDA and AMPA/Kainate Receptor Antagonists Against Ethambutol Induced Retinal Toxicity Using Optomotor Response (OMR) in Goldfish

ABSTRACT

Objective: Ethambutol (EMB) is known to cause ocular toxicity on prolonged use. The present studyevaluated the effect of NMDA and AMPA/Kainate receptor antagonists(memantine & trimetazidine) againstethambutol induced ocular toxicity using Optomotor response (OMR) in goldfish.Materials and Methods: Either sex of goldfishes randomized into three groups (n=8 each group) and wereexposed to daily dose of ethambutol (1 mg/ml for one hour) for 26 days. Group 1 fishes received anintravitreal injection of 1 μl of normal saline. Group 2 and 3 fishes were given intravitreal injections of 20 μgmemantine (MEM) and 10 μg trimetazidine (TMZ) respectively at 10, 15, 20th and 25th day following anesthesia.After drug exposure, fishes OMR was evaluated, and pattern velocity was recorded (on 11, 16, 21st and 26thday) at 5 rpm in different light condition (blue, green and red).Results: Upon chronic exposure (1 hr in bathing solution / day) of ethambutol, at the dose of 1 mg/ml fishesshowed statistically significant decrease in percentage relative frequency (PRF) at 7th dayupon comparison to their baseline values on day 0. Significant decrease in PRF was observed in the greencolor (550 nm, p=0.002) and red color (605 nm, p=0.001) and this effect persisted up to 21st day. BothIndian J Physiol Pharmacol 2019; 63(4) 294–302*Corresponding authorDr. T. Velpandian, Professor & O/I, Ocular Pharmacology and Pharmacy Division, Dr. Rajendra Prasad Centre for OphthalmicSciences, All India Institute of Medical Sciences (AIIMS), New Delhi – 110029 (India); +91-11-26593162, +91-11-26588919;E-mail tvelpandian@hotmail.com(Received on Aug. 10, 2019) Indian J Physiol Pharmacol 2019; 63(4)NMDA Receptor and Ethambutol Induced Ocular Toxicity 295memantine and trimetazidine showed varying degrees of protection on 16th days against EMB induced oculartoxicity.Conclusion: Intravitreal administration of trimetazidine and memantine provide significant protection in thePRF-OMR, indicating the possibility of their use as a therapeutic intervention in the patients developingocular toxicity during antitubercular therapy (ATT).