Dynamics, alterations, and consequences of minimally invasive intraocular pressure elevation in rats.

ABSTRACT

PURPOSE: An important, yet not exclusive, aspect of primary open angle glaucoma is elevated intraocular pressure (IOP) profiles within fluctuations and pressure peaks. The study aimed at establishing minimally invasive methods for recurrent IOP elevation in rats to investigate the impact of IOP dynamics and pathomorphologic retinal alterations during and after IOP elevation. METHODS: Intraocular pressure was elevated unilaterally in Long Evans rats to a level of ≈35 mm Hg for 1 hour in a total of 30 manipulations within 6 weeks, by using two methods: (1) suction-cup oculopression and (2) loop-adjusted oculopression. Retinal thickness (RT) was measured via optical coherence tomography (OCT), and neuronal survival was analyzed. Additional experiments were performed for "in situ" OCT investigations during exposures to different IOP levels. RESULTS: A mean IOP exposure of +737.3 ± 9.6 ΔIOP mm Hg for loop adjustment and +188.9 ± 16 ΔIOP mm Hg for suction cup was achieved. Optical coherence tomography examination revealed notable changes of RT between controls, untreated, and treated eyes, and evaluation of neuronal loss showed a significant decrease of retinal ganglion cell (RGC) density in both groups. In situ OCT investigation showed paradoxical retinal distortion and deformation of the optic nerve head toward the eye background. CONCLUSIONS: After accurate IOP elevation with minimally invasive methods, it was possible to detect RGC loss and retinal thinning. While suction cup is capable of simulating accurate arbitrary IOP profiles, loop adjustment enables the detection of pressure-dependent retinal alterations. For the first time, it was feasible to investigate consequences of variable IOP elevation profiles, including pressure peaks, by using real-time live imaging in vivo.