Characterization of circumlimbal suture induced chronic ocular hypertension in albino rats anaesthetised under Ketamine-Xylazine or Isoflurane

Abstract

Purpose : The circumlimbal suture approach has been used for inducing chronic ocular hypertension (COH) in rodents. We considered whether this model also works in albino rats and if the anaesthesia at the time of model induction (ketamine-xylazine (KX) mixture and Isoflurane (ISO)) influences outcomes.

Methods : Sprague-Dawley rats (10 weeks old) anaesthetized with KX or ISO received a circumlimbal suture around both eyes. The suture on one randomly chosen eye was cut after day 1 (KX: n=16; ISO: n=12) to serve as the control. The suture on the treated COH eyes were left in place for 15 weeks (KX: n=16; ISO: n=11). IOP in awake rats was recorded twice a week (Tonolab). Changes (mean±SE) in retinal structure and function were subsequently assessed under KX (in both groups) at week 0, 4, 8, 12 and 15 using electroretinogram and optical coherence tomography, respectively.

Results : COH eyes showed significant IOP elevations of 4-8mmHg in KX and 3-5mmHg in ISO anesthetised rats between weeks 1 to 12 (p<0.05), there was a gradual reduction beyond 12 weeks. Positive scotopic threshold response (pSTR) amplitude were reduced (KX: 19+7% p>0.05; ISO: 21+9%; p=0.02) in COH eyes at weeks 8 and 12, with some recovery at week 15 in the KX group. Reductions in both b-wave (KX: 13+8% p>0.05; ISO: 19+8%; p=0.01) and a-wave responses (KX: 25+6%; ISO: 22+7%; p=0.01) at week 8 also showed recovery at week 15 in the KX group. A thinner retinal nerve fibre layer (RNFL) in the KX group was observed from week 4 (-7+3%; p=0.06) to week 12 (-6+4% from control eyes; p>0.05). As for the ISO group, RNFL thinning was noted at week 4 (-6+2%; p=0.06) and week 8 (-3+2% compared with control; p>0.05). Between weeks 12 to 15, total retinal thickness (5+1%; p<0.01) and outer retinal layer (7+1%; p<0.001) appeared to increase.

Conclusions : The circumlimbal suture model elevated IOP in albino rats regardless of the type of anaesthesia used during induction, resulting in similar structural and functional changes. There was mild RNFL thinning along with the reduction of ganglion cell function, that along with IOP reduction between weeks 12 and 15. Interestingly, a gradual thickening of outer retinal layer in sutured eyes has not been reported previously.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.