Effect of Strain on Rodent Glaucoma Models: Magnetic Bead Injection Versus Hydrogel Injection Versus Circumlimbal Suture

Abstract

Purpose To compare the inter-strain differences of three rodent glaucoma models as induced by magnetic bead injection, hydrogel injection, and circumlimbal suture. Methods In Brown Norway (BN) and Sprague Dawley (SD) rat strains, intraocular pressure (IOP) was elevated by injection of magnetic beads or hydrogel to obstruct the aqueous humor outflow or by external compression of circumlimbal suture. Maximum and average IOP values were compared according to both procedure and rat strain over 1 month postoperatively. Retinal ganglion cell (RGC) density loss was evaluated using confocal microscopic images of the flat-mounted retina obtained at postoperative days 14 and 30. Results The maximum IOPs were higher in the hydrogel injection or circumlimbal injection models than in the magnetic bead injection model ( P < 0.001), whereas average IOP showed no difference between the two strains (both P ≥ 0.05). A generalized estimating equation regression model showed that the IOP increase was maintained better in the BN rats than in the SD rats ( P < 0.001). Such inter-strain difference was smaller in the circumlimbal suture model. A significant decrease in RGC density was observed in all of the models for the BN rats and in the circumlimbal suture model for the SD rats at postoperative day 30. Conclusions BN rats were advantageous for the magnetic bead or hydrogel injection model, but either rat strain could be used for the circumlimbal suture model. Strains should be considered cautiously when establishing rodent glaucoma models with different IOP profiles. Translational Relevance This comparison offers the best strain for each rodent glaucoma model for assessment of glaucoma-relevant therapeutics.

Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists

“…Many animal models have been developed, characterized, and utilized to study the pathogenic elements of OHT and glaucoma [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ] ( Table 2 ). We chose to use the mouse in the present study.…”

“…Additionally, ≥30% of patients do not respond well to drug therapy, especially FP receptor agonists [1,16,17]. Uncontrolled elevated IOP and IOP spikes may even re- Many animal models have been developed, characterized, and utilized to study the pathogenic elements of OHT and glaucoma [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] (Table 2). We chose to use the mouse in the present study.…”