Selective ganglion cell functional loss in rats with experimental glaucoma.
OBJECTIVE
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 four to five times per week. After 5 weeks, animals were dark adapted overnight (>12 hours) and full-field electroretinograms (ERGs) were obtained simultaneously from both eyes. Scotopic ERG stimuli were brief white flashes (-6.64-2.72 log cd-s/m(2)). Photopic responses were also obtained (0.97-2.72 log cd-s/m(2)) after 15 minutes of light adaptation (150 cd/m(2)). Eyes were processed the following day for histologic 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 mm Hg, whereas the average for control eyes was 28.1 +/- 0.5 mm Hg (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 (r(2) = 0.78, P < 0.0001) and was unrelated to mean IOP in control eyes (r(2) = 0.09, P = 0.18). In experimental eyes with relatively mild IOP elevation (mean IOP < 31 mm Hg) and no structural (histologic) 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), whereas other ERG components remained unaltered. In four of the five eyes, pSTR amplitude was reduced by more than 50%, whereas all five had normal scotopic a-wave, b-wave, and OP amplitudes. Eyes with mean IOP of more than 35 mm Hg had reduced a-wave, b-wave, and oscillatory potential (OP) amplitudes.


CONCLUSIONS
As demonstrated by 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 before the onset of structural damage, as assessed by light microscopy of optic nerve tissue. The highest IOP levels resulted in nonselective functional loss. Thus, in rodent models of experimental glaucoma, lower levels of chronically elevated IOP may be more relevant to human primary chronic glaucoma.
Fortune
Brad
B
Discoveries in Sight, Devers Eye Institute, Legacy Health System, Portland, Oregon 97232, USA. bfortune@discoveriesinsight.org
Bui
Bang V
BV
Morrison
John C
JC
Johnson
Elaine C
EC
Dong
Jin
J
Cepurna
William O
WO
Jia
LiJun
L
Barber
Stacey
S
Cioffi
George A
GA
D000818:Animals; D003623:Dark Adaptation; D004195:Disease Models, Animal; D004596:Electroretinography; D005901:Glaucoma / Q000209:etiology / Q000503:physiopathology*; D007429:Intraocular Pressure; D008297:Male; D009798:Ocular Hypertension / Q000150:complications; D010775:Photic Stimulation; D051381:Rats; D011914:Rats, Inbred BN; D012165:Retinal Ganglion Cells / Q000502:physiology*