Abstract
Purpose:
To investigate the effect of intraocular pressure (IOP) lowering in a rat circumlimbal suture model of chronic ocular hypertension.
Methods:
Two groups of Long-Evans rats underwent unilateral suture (8/0) application around the equator of the eye to increase IOP. Contralateral eyes were untreated. In group-A (n=15), the suture was tied firmly and left in place for 15 weeks. IOP (3x/week) and electroretinography (ERG week-2, 4, 8, 12, 15) were measured. Group B (n=7), animals underwent the same procedure except the suture was removed at week-8 to normalise IOP. Anterior segment structures, retinal and retinal nerve fibre layer (RNFL) thickness were measured using SD-OCT at week-15, prior to tissue collection for counts of cells in the ganglion cell layer (H&E staining). ERG waveforms were analysed to return measures of photoreceptor (a-wave), bipolar cell (b-wave) and retinal ganglion cell (RGC, scotopic threshold response, STR) activity. Amplitudes were expressed relative (average%±SEM) to the contralateral untreated control eye.
Results:
IOP elevation over the first 8 weeks was similar (p=0.17) in groups A (14.4±0.9 to 22.3±1.4mmHg) and B (12.6±0.9 to 20.1±0.4mmHg). At week-8 groups-A and B showed similar a-wave (A:-9±1% vs B:-9±2%, p=0.89), b-wave (A:-10±3% vs B:-10±3%, p=0.96) and STR (A:-31±8% vs B:-32±12%, p=0.94) reductions. In group-B, after suture removal IOP recovered to normal (13.6±0.6mmHg) for the remainder of the experiment. At week-15 group-B showed partial STR recovery (back to -11±5%), whereas group-A continued to show STR loss. OCT revealed significant thinning of the retina (control 200.7±5.2 vs treated 187.4±4.2µm, p<0.01) and RNFL (control 21.7±0.4 vs treated 13.9±2.5µm, p<0.05) in group-A but not group-B (retina: control 201.1±3.5 vs treated 197.3±2.9µm, p=0.30; RNFL: control 21.6±0.6 vs treated 18.2±1.4µm, p=0.08). No significant change in anterior chamber angle and depth was noted in both groups. Cell number in the RGC layer was reduced in the treated eyes in group-A (4167±222 vs 1886±190/mm2, p<0.001), but not in group-B (4057±476 vs 3600±870/mm2, p=0.66).
Conclusions:
Chronic IOP elevation by circumlimbal suture in rats produces preferential inner retinal ERG loss, RNFL thinning and RGC loss. These changes can be reversed by IOP normalisation through cutting the suture at an early stage of this model.
Keywords: 510 electroretinography: non-clinical •
688 retina •
531 ganglion cells