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Retinal damage after 3 to 4 months of elevated intraocular pressure in a rat glaucoma model.
Invest Ophthalmol Vis Sci. 2000 Oct; 41(11):3451-9.IO

Abstract

PURPOSE

To characterize a long-term elevated intraocular pressure (IOP) glaucoma model in the rat with respect to electroretinographic (ERG) changes and the pattern and mechanism of retinal ganglion cell (RGC) death. METHODS; An approximate doubling of IOP was induced in one eye (G) of female Wistar rats (150-180 g) by cautery of 3 episcleral/limbal veins. At intervals over 3 to 4 months, measurements of IOP and ERG changes (contact-lens electrode) were made in both the G and contralateral normal (N) eyes. At the end of 3 to 4 months of elevated IOP, RGCs were fluorescently labeled with Fluorogold (retrogradely from the superior colliculus), or retinas were labeled by intravitreal injection of a mitochondrial potential indicator dye and stained for apoptotic nuclei with a DNA dye. Flatmounts of fixed, dye-labeled retinas were examined by epifluorescence, confocal, or interference contrast microscopy.

RESULTS

Elevated IOP was consistently maintained for up to 4 months in G eyes, but ERG a- and b-waves showed a statistically significant decline, of 30% to 40% in amplitude, after 3 months. Loss of RGCs in G retinas was primarily focal with no statistically significant loss demonstrable outside of the focal areas when assessed by an area sampling method for counting RGCs, which totaled 2% to 3% of the entire retinal area. Mitochondrial membrane potential of cells in the RGC layer was reduced by 17.5% (P: < 0.05) in regions surrounding areas of focal loss compared with comparable locations in control N eyes. After 3.5 months' elevated IOP the G retinas showed cell nuclei at various stages of apoptosis, from initial DNA condensation to fragmentation.

CONCLUSIONS

The three-vein episcleral/limbal vein occlusion model for inducing glaucomatous pathology in the rat eye gives a consistent long-term elevation of IOP. After 3 to 4 months of approximately 100% increased IOP, the ERG responses begin to decline, there is a variable focal loss of RGCs, and some of the remaining RGCs show characteristics of stress and apoptosis. These changes seem consistent with retinal damage in human glaucoma (focal field defects), and this rat model appears to mimic some features of primary open-angle glaucoma.

Authors+Show Affiliations

Departments of Ophthalmology and. Neurology, Mount Sinai School of Medicine, New York University, New York 10029-6574, USA. thomas.mittag@mssm.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11006238

Citation

Mittag, T W., et al. "Retinal Damage After 3 to 4 Months of Elevated Intraocular Pressure in a Rat Glaucoma Model." Investigative Ophthalmology & Visual Science, vol. 41, no. 11, 2000, pp. 3451-9.
Mittag TW, Danias J, Pohorenec G, et al. Retinal damage after 3 to 4 months of elevated intraocular pressure in a rat glaucoma model. Invest Ophthalmol Vis Sci. 2000;41(11):3451-9.
Mittag, T. W., Danias, J., Pohorenec, G., Yuan, H. M., Burakgazi, E., Chalmers-Redman, R., Podos, S. M., & Tatton, W. G. (2000). Retinal damage after 3 to 4 months of elevated intraocular pressure in a rat glaucoma model. Investigative Ophthalmology & Visual Science, 41(11), 3451-9.
Mittag TW, et al. Retinal Damage After 3 to 4 Months of Elevated Intraocular Pressure in a Rat Glaucoma Model. Invest Ophthalmol Vis Sci. 2000;41(11):3451-9. PubMed PMID: 11006238.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Retinal damage after 3 to 4 months of elevated intraocular pressure in a rat glaucoma model. AU - Mittag,T W, AU - Danias,J, AU - Pohorenec,G, AU - Yuan,H M, AU - Burakgazi,E, AU - Chalmers-Redman,R, AU - Podos,S M, AU - Tatton,W G, PY - 2000/9/28/pubmed PY - 2000/10/14/medline PY - 2000/9/28/entrez SP - 3451 EP - 9 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 41 IS - 11 N2 - PURPOSE: To characterize a long-term elevated intraocular pressure (IOP) glaucoma model in the rat with respect to electroretinographic (ERG) changes and the pattern and mechanism of retinal ganglion cell (RGC) death. METHODS; An approximate doubling of IOP was induced in one eye (G) of female Wistar rats (150-180 g) by cautery of 3 episcleral/limbal veins. At intervals over 3 to 4 months, measurements of IOP and ERG changes (contact-lens electrode) were made in both the G and contralateral normal (N) eyes. At the end of 3 to 4 months of elevated IOP, RGCs were fluorescently labeled with Fluorogold (retrogradely from the superior colliculus), or retinas were labeled by intravitreal injection of a mitochondrial potential indicator dye and stained for apoptotic nuclei with a DNA dye. Flatmounts of fixed, dye-labeled retinas were examined by epifluorescence, confocal, or interference contrast microscopy. RESULTS: Elevated IOP was consistently maintained for up to 4 months in G eyes, but ERG a- and b-waves showed a statistically significant decline, of 30% to 40% in amplitude, after 3 months. Loss of RGCs in G retinas was primarily focal with no statistically significant loss demonstrable outside of the focal areas when assessed by an area sampling method for counting RGCs, which totaled 2% to 3% of the entire retinal area. Mitochondrial membrane potential of cells in the RGC layer was reduced by 17.5% (P: < 0.05) in regions surrounding areas of focal loss compared with comparable locations in control N eyes. After 3.5 months' elevated IOP the G retinas showed cell nuclei at various stages of apoptosis, from initial DNA condensation to fragmentation. CONCLUSIONS: The three-vein episcleral/limbal vein occlusion model for inducing glaucomatous pathology in the rat eye gives a consistent long-term elevation of IOP. After 3 to 4 months of approximately 100% increased IOP, the ERG responses begin to decline, there is a variable focal loss of RGCs, and some of the remaining RGCs show characteristics of stress and apoptosis. These changes seem consistent with retinal damage in human glaucoma (focal field defects), and this rat model appears to mimic some features of primary open-angle glaucoma. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/11006238/Retinal_damage_after_3_to_4_months_of_elevated_intraocular_pressure_in_a_rat_glaucoma_model_ L2 - https://iovs.arvojournals.org/article.aspx?volume=41&amp;issue=11&amp;page=3451 DB - PRIME DP - Unbound Medicine ER -