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R. Iezzi, I. Glybina, B. Raja Guru, A. Kennedy, R. Kannan; Dendrimer-Fluocinolone Acetonide Nanodevices Supress Retinal Neuroinflammation and Are Neuroprotective in RCS Rats. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2411.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the efficacy of intravitreal dendrimer-conjugated fluocinolone acetonide (D-FA) nanodevices in slowing photoreceptor cell loss in the RCS rat retinal degeneration model.
30 albino homozygous RCS rats aged 5 weeks were divided into 6 equal groups, 1.0 µg D-FA, 3.0 µg D-FA, 1.0 µg fluocinolone acetonide (FA), 3.0 µg FA, phosphate buffered saline (PBS)/DMSO vehicle control and light-exposed controls. A volume of 1.0 µL PBS with 5% DMSO was used as the solvent for all injections. Full-field scotopic flash electroretinography at 25 cd-Sec/M2 was performed prior to injection at baseline and weekly over the 4-week study. Photoreceptor cell counts were obtained via quantitative histology four-weeks after injection at postnatal week nine.
ERG b-wave amplitudes were significantly preserved in all groups that received FA, relative to controls (p = 0.04 to 5x10-8). ERG a-wave amplitudes were significantly greater for both D-FA doses and 3.0 µg unconjugated FA as compared to controls (p = 0.04 to 1x10-11). D-FA 1.0 µg and 3.0 µg demonstrated significantly better preservation of a-wave and b-wave amplitudes as compared to unconjugated FA at 1.0 µg and 3.0 µg doses (b-wave:p = 0.04 to 1.7x10-6, a-wave:p = 0.004 to 2.2x10-7). Quantitative histological analysis revealed that mean outer nuclear layer cell (ONL) counts for D-FA 3.0µg were 73.6±14.2, 72.2±9.0 for D-FA 1.0µg, 55.38±9.5 for FA 3.0µg and 40.1±18.0 for FA 1.0µg. Both D-FA doses resulted in statistically higher ONL cell counts than those of the PBS (mean=48±11) and control (mean=32.6±10.2) groups (D-FA 3.0µg:p=0.01 vs PBS, p<0.001 vs control, D-FA 1.0µg:p=0.01 vs PBS, p<0.001 vs control).
FA is neuroprotective in RCS rats during the peak period of photoreceptor degeneration, from weeks five through nine. D-FA demonstrated statistically significant improvements in neuroprotection over non-conjugated FA. Dendrimer conjugation of FA is a novel drug delivery platform for retinal neuroprotection in photoreceptor degeneration.
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