title: Characterization of retinal damage in the episcleral vein cauterization rat glaucoma model.
abstract: Episcleral vein cauterization (EVC) is used in rats to generate a glaucoma model with high intraocular pressure (IOP). The long-term retinal damage in this glaucoma model, however, has not been accurately quantified. We report the location and amount of retinal ganglion cell (RGC) damage caused by (EVC) induced IOP elevation in two rat strains. IOP was raised in one eye of Wistar (N = 5) and Brown-Norway(B-N)(N = 7) rats by EVC and monitored monthly until IOP in contralateral eyes equalized at 5 months post-surgery. Animals were maintained for 3.5-4.5 additional months. B-N rats (N = 7) that had no EVC served as controls for this strain. Scotopic flash ERGs were recorded at baseline and just prior to euthanasia. Automated counts of all retrogradely labeled RGCs in retinal flat-mounts were determined and compared between contralateral eyes. RGC density maps were constructed and RGC size distribution was determined. Oscillatory potentials in the group of eyes which had elevated IOP were decreased at the time of euthanasia, when IOP had returned to normal. The group of normal B-N rats had similar RGC counts between contralateral eyes. In the experimental group the mean number of RGCs was not significantly different between control and experimental eyes, but 1 of 5 Wistar and 2 of 7 B-N experimental eyes had at least 30% fewer RGCs than contralateral control eyes. Total retinal area in B-N experimental eyes was higher compared to contralateral eyes. Cumulative IOP exposure of the experimental eyes was modestly correlated with RGC loss while oscillatory potentials appeared to be inversely related to RGC loss. In retinas with extensive (> 30% RGC loss) but not complete damage, smaller cells were preserved better than larger ones. The above results indicate that RGC loss in both Wistar and B-N strains is variable after a prolonged elevation of IOP via EVC. Such variability despite equivalent IOP levels and ERG abnormalities, suggests unknown factors that can protect IOP-stressed RGCs. Identification and enhancement of such factors could prove useful for glaucoma therapy.
authors.affiliation: Department of Ophthalmology, Mt Sinai School of Medicine, Box 1183, 1 Gustave L Levy Place, New York, NY 10029, USA. john.danias@mssm.edu
authors.forename: John
authors.initials: J
authors.lastname: Danias
authors.forename: Fran
authors.initials: F
authors.lastname: Shen
authors.forename: Manolis
authors.initials: M
authors.lastname: Kavalarakis
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Goldblum
authors.forename: Kevin
authors.initials: K
authors.lastname: Lee
authors.forename: Maria-Florencia
authors.initials: MF
authors.lastname: Zamora
authors.forename: YanLing
authors.initials: Y
authors.lastname: Su
authors.forename: Scott E
authors.initials: SE
authors.lastname: Brodie
authors.forename: Steven M
authors.initials: SM
authors.lastname: Podos
authors.forename: Thom
authors.initials: T
authors.lastname: Mittag
mesh_terms: D000818:Animals; D002425:Cautery; D002452:Cell Count; D004596:Electroretinography; D005260:Female; D005901:Glaucoma / Q000473:pathology*; D007090:Image Interpretation, Computer-Assisted; D007429:Intraocular Pressure; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D051381:Rats; D011914:Rats, Inbred BN; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000473:pathology*; D012590:Sclera / Q000098:blood supply; D014680:Veins