Selective loss of the electroretinogram scotopic threshold response (STR) at low levels of elevated intraocular pressure in a rat model of experimental glaucoma

Abstract

Abstract: : Purpose: To characterize retinal functional consequences of elevated intraocular pressure (IOP) in a rat model of experimental glaucoma. Methods: Unilateral elevation of IOP was produced by hypertonic saline injection into an episcleral vein in 20 adult male Brown–Norway rats. IOP was measured in both eyes of awake animals several (4–5) times per week. After 5 weeks, animals were dark adapted overnight (>12 h) and full–field electroretinograms (ERGs) were obtained simultaneously from both eyes. Scotopic ERG stimuli were brief white flashes (–6.64 to 2.72 log cd s m^–2). Photopic responses were also obtained (0.97 to 2.72 log cd s m^–2) after 15 minutes of light adaptation (150 cd m^–2). Eyes were processed the following day for histological evaluation by light microscopy, including masked determination of optic nerve injury grade (ONIG, 1 = normal; 5 = severe, diffuse damage). Results: Among experimental eyes, the group average IOP (±SD) was 34.5 ± 4.1, while the average for control eyes was 28.1 ± 0.5 (t = 7.1, p < 0.0001). The average ONIG for experimental and control eye groups, respectively, was 3.4 ± 1.7 and 1.0 ± 0.02 (t = 6.3, p < 0.0001). The ONIG increased with mean IOP in experimental eyes (r² = 0.78, p < 0.0001), and was unrelated to mean IOP in control eyes (r² = 0.09, p = 0.18). In experimental eyes with relatively mild IOP elevation (mean IOP < 31 mm Hg) and no structural (histological) damage to the optic nerve evident by light microscopy (ONIG = 1.1 ± 0.2, n = 5), there was a selective reduction of the positive scotopic threshold response (pSTR, p < 0.001), while other ERG components remained unaltered. In 4 of these 5 eyes, pSTR amplitude was reduced by > 50%, while all 5 had normal scotopic a–wave, b–wave and OP amplitudes. Eyes with mean IOP > 35 mm Hg had reduced a–wave, b–wave and OP amplitudes. Conclusions: As demonstrated by our prior studies, selective loss of the pSTR is indicative of selective retinal ganglion cell (RGC) injury. In this rat model of experimental glaucoma, selective RGC functional injury occurred prior to the onset of structural damage as assessed by light microscopy of optic nerve tissue. The highest IOP levels resulted in non–selective functional loss. Thus, in rodent models of experimental glaucoma, lower levels of chronically elevated IOP may be more relevant to human primary chronic glaucoma.

Keywords: intraocular pressure • electroretinography: clinical • ganglion cells