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R. Iezzi, I. V. Glybina, A. Kennedy, P. Ashton, G. W. Abrams; Fluocinolone Acetonide-Mediated Neuroprotection in S334-ter-4 Rat Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2036.
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© ARVO (1962-2015); The Authors (2016-present)
To study neuroprotective effects of intravitreal fluocinolone acetonide (FA) in albino S334-ter-4 rats.
S334ter rats aged four-weeks were divided into four groups: 0.5µg/day FA-loaded intravitreal drug-delivery implant (IDDI); 0.2µg/day FA-loaded IDDI; inactive IDDI; and unoperated controls. Electroretinography (ERG) and intraocular pressure (IOP) measurements were performed pre-operatively and every two weeks post-operatively. At twelve weeks, animals were sacrificed. Outer nuclear layer (ONL) and inner nuclear layer (INL) thicknesses were measured. ED-1 antibody-labelled microglial cell processes were counted. Total microglial cell counts were made via IBA-1 immunohistochemical staining in retina wholemounts.
After an eight week study period, inactive IDDI and unoperated S334ter rats demonstrated 50-60% reduction in ERG a- and b-wave amplitudes (p<0.001 for both groups). FA 0.2µg/day animals demonstrated 15% amplitude attenuations and FA 0.5µg/day animals a 30% reduction in a- and b-wave amplitudes. IOP remained normal. ONL thickness in FA 0.2µg/day-treated eyes was 25.8%±2.3% higher than in control group eyes (p<0.001) and 30.0%±2.1% higher than in IDDI-implanted eyes (p<0.001). In FA 0.5µg/day-treated eyes, ONL cell counts were 22.4%±2.8% higher than in control group eyes (p<0.001) and 22.3%±3.7% higher than in IDDI-implanted eyes (p<0.01). There was no statistically significant difference between unoperated control and IDDI-implanted control groups. No statistically significant difference between the two treated groups was found. INL cell counts did not show statistically significant differences across experimental groups. FA-treated groups demonstrated significantly fewer activated microglial cells and overall number of microglia in the photoreceptors, compared to control groups.
Chronic intravitreal infusion of FA is neuroprotective in S334ter rats, preserves ONL cell morphology and ERG a- and b-wave amplitudes and reduces retinal neuroinflammation. Based on these findings, chronic intravitreal delivery of FA may have a therapeutic role in patients with retinitis pigmentosa.
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