Selective ganglion cell functional loss in rats with experimental glaucoma

Brad Fortune, Bang V. Bui, John Morrison, Elaine Johnson, Jin Dong, William O. Cepurna, LiJun Jia, Stacey Barber, George A. Cioffi

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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 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/m2). Photopic responses were also obtained (0.97-2.72 log cd-s/m2) after 15 minutes of light adaptation (150 cd/m2). 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 (r2 = 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.

Original languageEnglish (US)
Pages (from-to)1854-1862
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume45
Issue number6
DOIs
StatePublished - Jun 2004

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Intraocular Pressure
Ganglia
Glaucoma
Microscopy
Theoretical Models
Retinal Ganglion Cells
Optic Nerve
Light
Optic Nerve Injuries
Ocular Adaptation
Nerve Tissue
Wounds and Injuries
Veins
Rodentia
Control Groups
Injections

ASJC Scopus subject areas

  • Ophthalmology

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Selective ganglion cell functional loss in rats with experimental glaucoma. / Fortune, Brad; Bui, Bang V.; Morrison, John; Johnson, Elaine; Dong, Jin; Cepurna, William O.; Jia, LiJun; Barber, Stacey; Cioffi, George A.

In: Investigative Ophthalmology and Visual Science, Vol. 45, No. 6, 06.2004, p. 1854-1862.

Research output: Contribution to journalArticle

Fortune, Brad ; Bui, Bang V. ; Morrison, John ; Johnson, Elaine ; Dong, Jin ; Cepurna, William O. ; Jia, LiJun ; Barber, Stacey ; Cioffi, George A. / Selective ganglion cell functional loss in rats with experimental glaucoma. In: Investigative Ophthalmology and Visual Science. 2004 ; Vol. 45, No. 6. pp. 1854-1862.
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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 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/m2). Photopic responses were also obtained (0.97-2.72 log cd-s/m2) after 15 minutes of light adaptation (150 cd/m2). 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 (r2 = 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.",
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T1 - Selective ganglion cell functional loss in rats with experimental glaucoma

AU - Fortune, Brad

AU - Bui, Bang V.

AU - Morrison, John

AU - Johnson, Elaine

AU - Dong, Jin

AU - Cepurna, William O.

AU - Jia, LiJun

AU - Barber, Stacey

AU - Cioffi, George A.

PY - 2004/6

Y1 - 2004/6

N2 - 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 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/m2). Photopic responses were also obtained (0.97-2.72 log cd-s/m2) after 15 minutes of light adaptation (150 cd/m2). 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 (r2 = 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.

AB - 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 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/m2). Photopic responses were also obtained (0.97-2.72 log cd-s/m2) after 15 minutes of light adaptation (150 cd/m2). 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 (r2 = 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.

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