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Correlation between retinal ganglion cell death and chronically developing inherited glaucoma in a new rat mutant.
Exp Eye Res. 2004 Jul; 79(1):119-29.EE

Abstract

Glaucoma is a progressive optic neuropathy with characteristic optic disc changes, retinal ganglion cell loss and progressive visual field defects. Elevated intraocular pressure is considered to be a major risk factor in glaucomatous neuropathy. This study aimed to characterize and document a new chronic glaucoma model in the rat with respect to the effect of elevated intraocular pressure on overall retinal dysfunction and retinal ganglion cell loss, and to elucidate the possible mechanisms underlying this cell loss. Intraocular pressure (IOP) was measured in rats using a Tonopen. RGCs were retrogradely labeled with the fluorescent dye, 4-[didecylaminostyryl]-N-methyl-pyridinium-iodide (4-Di-10 ASP) and quantified on retinal flat mounts using fluorescence microscopy. The optic nerve head was examined fundoscopically. Changes in the histological appearance of the whole eyes was studied in paraffin sections, and immunohistochemistry was carried out on cryostat sections. The levels of mRNA for several genes were compared between control and glaucomatous retinae using semi-quantitative RT-PCR. Mutant animals are affected with either a unilateral or bilateral enlargement of the globes having an IOP that ranged from 25 to 45 mmHg, as compared to control values of 12-16 mmHg. The IOP of glaucomatous eyes increased significantly with age to attain a value of 35+/-7.3 at 1.5 years. Concomitant with the rise in IOP, the number of labeled RGCs continued to decrease in number with age. A total of 1887+/-117RGC mm(-2) could be labeled in wild-type control and juvenile mutant pre-glaucomatous retinas, whereas this number dropped to 92+/-26RGC mm(-2) at 1.5 years. Ophthalmoscopy revealed atrophied optic nerve heads in the affected eyes. The pars plicata and the pars plana of the ciliary body of glaucomatous eyes were hypertrophied and elongated, respectively. The anterior chamber was narrow and the irido-corneal angle open in glaucoma eyes. The mRNA of glial-fibrillary-acidic protein, endothelin-1, STAT-3 and STAT-6 increased in the retinas correlating with the severity and duration of the disease. Changes in the expression of GFAP and endothelin-1 could be confirmed using immunohistochemistry. This model may help to address several fundamental issues in the pathogenesis of glaucoma and aid in the development of neuroprotective strategies.

Authors+Show Affiliations

Department of Experimental Ophthalmology, School of Medicine, University Eye Hospital Münster, Domagkstrasse 15, D-48149 Münster, Germany. solon@uni-muenster.deNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15183107

Citation

Thanos, Solon, and Rita Naskar. "Correlation Between Retinal Ganglion Cell Death and Chronically Developing Inherited Glaucoma in a New Rat Mutant." Experimental Eye Research, vol. 79, no. 1, 2004, pp. 119-29.
Thanos S, Naskar R. Correlation between retinal ganglion cell death and chronically developing inherited glaucoma in a new rat mutant. Exp Eye Res. 2004;79(1):119-29.
Thanos, S., & Naskar, R. (2004). Correlation between retinal ganglion cell death and chronically developing inherited glaucoma in a new rat mutant. Experimental Eye Research, 79(1), 119-29.
Thanos S, Naskar R. Correlation Between Retinal Ganglion Cell Death and Chronically Developing Inherited Glaucoma in a New Rat Mutant. Exp Eye Res. 2004;79(1):119-29. PubMed PMID: 15183107.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Correlation between retinal ganglion cell death and chronically developing inherited glaucoma in a new rat mutant. AU - Thanos,Solon, AU - Naskar,Rita, PY - 2003/11/25/received PY - 2004/02/04/accepted PY - 2004/6/9/pubmed PY - 2004/8/31/medline PY - 2004/6/9/entrez SP - 119 EP - 29 JF - Experimental eye research JO - Exp Eye Res VL - 79 IS - 1 N2 - Glaucoma is a progressive optic neuropathy with characteristic optic disc changes, retinal ganglion cell loss and progressive visual field defects. Elevated intraocular pressure is considered to be a major risk factor in glaucomatous neuropathy. This study aimed to characterize and document a new chronic glaucoma model in the rat with respect to the effect of elevated intraocular pressure on overall retinal dysfunction and retinal ganglion cell loss, and to elucidate the possible mechanisms underlying this cell loss. Intraocular pressure (IOP) was measured in rats using a Tonopen. RGCs were retrogradely labeled with the fluorescent dye, 4-[didecylaminostyryl]-N-methyl-pyridinium-iodide (4-Di-10 ASP) and quantified on retinal flat mounts using fluorescence microscopy. The optic nerve head was examined fundoscopically. Changes in the histological appearance of the whole eyes was studied in paraffin sections, and immunohistochemistry was carried out on cryostat sections. The levels of mRNA for several genes were compared between control and glaucomatous retinae using semi-quantitative RT-PCR. Mutant animals are affected with either a unilateral or bilateral enlargement of the globes having an IOP that ranged from 25 to 45 mmHg, as compared to control values of 12-16 mmHg. The IOP of glaucomatous eyes increased significantly with age to attain a value of 35+/-7.3 at 1.5 years. Concomitant with the rise in IOP, the number of labeled RGCs continued to decrease in number with age. A total of 1887+/-117RGC mm(-2) could be labeled in wild-type control and juvenile mutant pre-glaucomatous retinas, whereas this number dropped to 92+/-26RGC mm(-2) at 1.5 years. Ophthalmoscopy revealed atrophied optic nerve heads in the affected eyes. The pars plicata and the pars plana of the ciliary body of glaucomatous eyes were hypertrophied and elongated, respectively. The anterior chamber was narrow and the irido-corneal angle open in glaucoma eyes. The mRNA of glial-fibrillary-acidic protein, endothelin-1, STAT-3 and STAT-6 increased in the retinas correlating with the severity and duration of the disease. Changes in the expression of GFAP and endothelin-1 could be confirmed using immunohistochemistry. This model may help to address several fundamental issues in the pathogenesis of glaucoma and aid in the development of neuroprotective strategies. SN - 0014-4835 UR - https://www.unboundmedicine.com/medline/citation/15183107/Correlation_between_retinal_ganglion_cell_death_and_chronically_developing_inherited_glaucoma_in_a_new_rat_mutant_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014483504000600 DB - PRIME DP - Unbound Medicine ER -