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 author :Dr. 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).
ABSTRACT
An appropriate model to predict the effect of xenobiotics on the vision perception in neuropsychopharmacological studies is of great importance in drug development and toxicity studies. The present study evaluated the effect of CNS stimulant, depressant and therapeutic agents known to have ocular toxicity on optomotor response (OMR) using goldfish in a newly developed device. A digital light processing aided gyrating poly-chromatic dotted pattern-OMR (Gyro-dot-OMR) analyzer was developed and standardized for this study in our laboratory. Goldfishes were exposed to varying concentrations of caffeine and pentobarbitone sodium to evaluate the effect of CNS stimulation and depression on OMR in white light. Ethambutol induced ocular toxicity was evaluated by intravitreal injection into both eyes of goldfishes. They were subjected for polychromatic Gyro-dot-OMR in both clock and anticlockwise directions. At the low concentration (5, 10 and 20 ng/mL) caffeine exposed animals showed significant (p<0.05) stimulant effect and the EC50 of caffeine in goldfish was found to be 4.806 ng/mL. In contrast, pentobarbitone sodium treated fishes showed significant (p<0.05) depressant effect with increasing the concentration. Ethambutol toxicity was reflected by the color discrimination in the Gyro-dot-OMR pattern. For the first time, this model proved the possibility of running Irwin profile test on goldfish using Gyro-dot-OMR. This model successfully predicted ethambutol induced toxicity with poor discrimination of red-green color. This model can be used for predicting toxicity of drugs affecting vision perception.