Abstract
Purpose:
Patients suffering from primary open angle glaucoma show fluctuating intraocular pressure (IOP) profiles within circadian variations and pressure peaks. To investigate the pathological role, an animal model with selectable IOP adjustment is needed. The presented study aimed for establishing a minimal-invasive method for controlled IOP elevation in rats based on suction-cup oculopression and examined basic properties of IOP dynamics and glaucomatous-like alterations.
Methods:
Suction-cup oculopression method reduces the globe range by sucking the cornea into a cup (Ø 0.4 mm). IOP elevation theoretically depends on cup diameter and correlates to the applied negative pressure in a mercury column. Manipulations were performed unilateral in nine Long-Evans rats at -100, -200, -300, -400 and -500 mmHg under Medetomidine sedation. To investigate IOP dynamics, IOP values in mmHg were recorded every five minutes during one hour. Eyes were examined for global glaucomatous alterations, retinal thickness and morphological changes of the optic nerve head via Spectralis OCT®. Post-Hoc tests of IOP data were performed.
Results:
IOP could easily be elevated using the cup-suction method. The observed averaged IOP of 16.5±3.4 at -100 mmHg negative pressure showed a significant increase compared to basic IOP values of 12.2±1.8 under sedation (p<0.02). Further pressure elevation to -200 mmHg lead to significant IOP elevation of 20.8±5.6 (p<0.0001), likewise -200 to -300, IOP was 27.6±6.7 and p<0.0001. Again, elevation to -400 revealed a significant IOP addition to 30.9±10.6 (p=0.01). Exertion of -500 mmHg did not cause further IOP elevation. IOP values of each elevation up to -400 are linear related to the negative pressure level with y=0.0485x+11.91, R^2=0.99. Eye examination exposed glaucomatous-like characteristics as fundus alteration, slight iris and ciliary alteration. Even after ten IOP elevation cycles, OCT examination showed a decrease of 1.6% of the retinal thickness between manipulated eye (188,2±13.5 µm) and the untreated (191.2±14.4 µm, p=0.13).
Conclusions:
This minimal-invasive model is suitable to simulate arbitrary profiles of IOP elevation with glaucomatous effects. Pressure elevation depends on cup size and negative pressure level, while Ø 0.4 mm cup works sufficient up to -400. Specific setups changes elicited phenotypic acute angle closure glaucoma with high IOP values and ciliar flushes.
Keywords: 568 intraocular pressure •
551 imaging/image analysis: non-clinical •
637 pathology: experimental