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I.V. Glybina, R. Iezzi, P. Ashton, G. Abrams; Neuroprotective Properties of Fluocinolone Acetonide Chronically Delivered into the Vitreous of Albino RCS Rats . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1028.
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© ARVO (1962-2015); The Authors (2016-present)
To study the neuroprotective effects of chronic intravitreal Fluocinolone Acetonide (FA) delivery in albino Royal College of Surgeons (RCS) rats.
20 albino RCS rats aged 5 weeks were used in the study: 5 received 0.5µg/day FA–loaded intravitreal drug–delivery implant (IDDI); (5) 0.2µg/day FA–loaded IDDI; (5) inactive IDDI (placebo); and (5) unoperated controls. Surgery was performed on one eye in each animal, under sterile conditions, using isoflurane mask anesthesia. The IDDIs and the injectors for their intravitreal implantation were a gift of Control Delivery Systems (Watertown, MA). Pre–operatively and each week for four–weeks, post–operatively, animals were followed via funduscopic exam, full–field electroretinography (ERG), and intraocular pressure (IOP) measurements. At the age of 9 weeks, animals were euthanized and retinal histology was performed in all eyes. ERG amplitudes and histological cell counts were statistically analyzed using one way ANOVA with concomitant paired t–testing when valid.
No statistically significant reductions of ERG b–wave amplitudes were observed in animals treated with both FA 0.2µg/day (pre: 0.595±0.1µV, post: 0.513±0.1µV, p=0.251) and FA 0.5µg/day (pre: 0.605±0.12µV, post: 0.347±0.22µV, p=0.074) throughout the post–operative period. Placebo–treated (pre: 0.638±0.17µV, post: 0.122±0.08µV, p<0.001) and unoperated RCS rats (pre: 0.538±0.11µV, post: 0.099±0.03µV, p<0.001) demonstrated dramatically reduced ERG b–wave amplitudes over the four week study. Postoperative alterations of IOP were not observed. Quantitative histological analysis showed that in the FA 0.2µg/day–treated eyes the outer nuclear layer (ONL) cell counts were 64.75±14.25% greater than in the untreated controls (p<0.001) and 3.96 times higher than in the placebo–treated eyes (p<0.001). In the FA 0.5µg/day–treated eyes the ONL cell counts were 44.2±27% greater relative to the unoperated control eyes (p<0.001) and 2.75 times higher relative to the placebo–treated eyes (p<0.001).
Chronic intravitreal infusion of FA was neuroprotective in RCS rats and preserved ONL cell counts and ERG b–wave amplitudes. Based on these findings, chronic intravitreal delivery of FA may have a therapeutic role in retinitis pigmentosa. In addition, since preservation of the ONL is associated with lower electrophosphene thresholds, this drug may improve the long–term function of retinal prosthetic devices.
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