Hsin-Hua Liu, Christine TO Nguyen, Bang V Bui, Algis J Vingrys, Zheng He

Purpose:
To develop a reliable and cost-effective animal model of chronic ocular hypertension which mimics glaucomatous optic neuropathy.

Method:
Long-Evans rats were anaesthetised (ket-amine/xylazine) and subjected to unilateral circum-limbal ligation through the conjunctiva (8-0 suture) to raise intraocular pressure (IOP), whereas the fellow untreated eye served as a control (n = 9). The sham treated group (n = 9) received the same treatment except the suture was loosely placed. IOP was moni-tored pre- and post-ligation for 4 weeks. Electroreti-nography (ERG) and fundus photography were recorded every two weeks to assess retinal function and gross morphology, respectively. ERG amplitudes were expressed relative to the contralateral untreated control eye (% ± SEM).

Results:
After 4 weeks, IOP was raised from 16.9 ± 0.8 to 21.1 ± 0.7 mm Hg in the treated eyes (p < 0.05) whilst the control (baseline 16.4 ± 0.9, week 4 12.3 ± 0.2 mm Hg) and sham eyes (baseline 15.6 ± 0.8, week 4 12.7 ± 0.2 mm Hg) remained unaltered (p > 0.05). Ocular hypertension for 4 weeks induced a greater reduction in ganglion cell response (Scotopic Thresh-old Response ?27 ± 7%) than the bipolar cell (b-wave ?18 ± 7%) and photoreceptor responses (a-wave ?18 ± 7%; p < 0.05). ERG components were unaltered in the sham treated (a-wave ?4 ± 5, b-wave ?9 ± 5, STR 0 ± 11%) eyes. Consistent with ganglion cell dysfunc-tion in the treated eyes, retinal photography showed reduced visibility of retinal nerve fibre bundles. Conclusion: Circumlimbal ligation provides a simple and cost-effective way to induce mild chronic ocular hypertension that produces preferential ganglion cell dysfunction. This model may be useful in glaucoma research.