Abstract
Purpose::
To characterize retinal function by full-field flash electroretinography in a mouse model of glaucoma, and to determine the relationship between the positive and negative scotopic threshold responses (STRs) and specific parameters of the intraocular pressure (IOP) profile.
Methods::
Following intravenous indocyanine green administration (40 mg/kg) unilateral chronic ocular hypertension was induced in 31 anaesthetized C57BL6/J mice by ablation of the limbal episcleral veins with an 810 nm laser. IOP measurements and scotopic full-field flash electroretinograms (ERG) were recorded after 5, 10, 20 and 40 days. Changes in inner retinal function were compared with specific parameters of the IOP profile: (i) peak IOP (maximum IOP at any time point), (ii) IOP difference (arithmetic difference in the IOP of treated and non-treated eyes at the time of ERG) and (iii) positive integral (arithmetic difference between the IOP.time curve integrals of the treated and non-treated eye). Ganglion cell apoptosis was assessed by cleaved caspase-3 immunohistochemistry and TUNEL. Ganglion cell density was quantified by Brn-3 immunohistochemistry.
Results::
Mean preoperative IOP was 17.9±0.1 mmHg (n=31). Laser treatment significantly elevated the IOP to 30.0±0.9 mmHg at 5 days (n=16) and 27.2±1.4 mmHg at 40 days (n=7) and caused selective and progressive apoptotic loss of ganglion cells. IOP elevation induced preferential inhibition of the STRs. The positive STR was the most susceptible ERG component, being maximally suppressed by 68% at day 5. The STR suppression correlated with the peak IOP and IOP difference parameters. At each time point, the magnitude of STR suppression exceeded the quantified ganglion cell loss.
Conclusions::
In our model, elevated IOP causes selective inner retinal dysfunction that precedes ganglion cell death.
Keywords: intraocular pressure • electroretinography: non-clinical • ganglion cells