In vivo toxicity study of rhodamine 6G in the rat retina

TY - JOUR

T1 - In vivo toxicity study of rhodamine 6G in the rat retina

AU - Thaler, Sebastian

AU - Haritoglou, Christos

AU - Choragiewicz, Tomasz J

AU - Messias, Andre

AU - Baryluk, Aneta

AU - May, C Albrecht

AU - Rejdak, Robert

AU - Fiedorowicz, Michal

AU - Zrenner, Eberhart

AU - Schuettauf, Frank

PY - 2008/5

Y1 - 2008/5

N2 - PURPOSE: To investigate the intraocular effect of rhodamine 6G (R6G) on retinal structures and function in an in vivo rat model and to develop an in vivo method for accurate evaluation of new dyes for intraocular surgery.METHODS: R6G in physiologic saline solution (PSS) was injected into the vitreous of adult Brown Norway rats at concentrations of 0.0002%, 0.002%, 0.02%, 0.2%, and 0.5%. Control animals received only PSS. Retinal toxicity was assessed by retinal ganglion cell (RGC) counts, light microscopy 7 days later, photopic electroretinography (ERG), and measurement of scotopic sensitivity and recovery of dark adaptation 48 hours and 7 days after intravitreous injection.RESULTS: R6G at concentrations of 0.2% and 0.5% led to a dose-dependent loss of RGC. The most significant loss occurred at 0.5%. Lower concentrations (0.0002%, 0.002%, and 0.02%) produced no statistically significant retinal ganglion cell loss. Analysis of the eyes by light microscopy showed no structural changes in the central retina, although injections of 0.5% R6G were followed by impressive degenerative changes adjacent to the injection sites. ERGs showed no effects of the highest R6G concentration on rods, kinetics of rhodopsin recovery after bleaching, or cone-driven responses.CONCLUSIONS: R6G can be safely injected in doses of up to 0.02% in rats, but has a toxic effect on retinal ganglion cells at higher concentrations. Accumulation of R6G may be a problem at higher concentrations, particularly at the injection site.

AB - PURPOSE: To investigate the intraocular effect of rhodamine 6G (R6G) on retinal structures and function in an in vivo rat model and to develop an in vivo method for accurate evaluation of new dyes for intraocular surgery.METHODS: R6G in physiologic saline solution (PSS) was injected into the vitreous of adult Brown Norway rats at concentrations of 0.0002%, 0.002%, 0.02%, 0.2%, and 0.5%. Control animals received only PSS. Retinal toxicity was assessed by retinal ganglion cell (RGC) counts, light microscopy 7 days later, photopic electroretinography (ERG), and measurement of scotopic sensitivity and recovery of dark adaptation 48 hours and 7 days after intravitreous injection.RESULTS: R6G at concentrations of 0.2% and 0.5% led to a dose-dependent loss of RGC. The most significant loss occurred at 0.5%. Lower concentrations (0.0002%, 0.002%, and 0.02%) produced no statistically significant retinal ganglion cell loss. Analysis of the eyes by light microscopy showed no structural changes in the central retina, although injections of 0.5% R6G were followed by impressive degenerative changes adjacent to the injection sites. ERGs showed no effects of the highest R6G concentration on rods, kinetics of rhodopsin recovery after bleaching, or cone-driven responses.CONCLUSIONS: R6G can be safely injected in doses of up to 0.02% in rats, but has a toxic effect on retinal ganglion cells at higher concentrations. Accumulation of R6G may be a problem at higher concentrations, particularly at the injection site.

KW - Animals

KW - Cell Count

KW - Dark Adaptation

KW - Dose-Response Relationship, Drug

KW - Electroretinography/drug effects

KW - Fluorescent Dyes/administration & dosage

KW - Male

KW - Oscillometry

KW - Rats

KW - Rats, Inbred BN

KW - Retina/drug effects

KW - Retinal Degeneration/chemically induced

KW - Retinal Ganglion Cells/drug effects

KW - Rhodamines/administration & dosage

U2 - 10.1167/iovs.07-1476

DO - 10.1167/iovs.07-1476

M3 - SCORING: Journal article

C2 - 18436844

VL - 49

SP - 2120

EP - 2126

JO - INVEST OPHTH VIS SCI

JF - INVEST OPHTH VIS SCI

SN - 0146-0404

IS - 5

ER -