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Originally published In Press as doi:10.1167/iovs.08-2831 on April 30, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:4847-4857.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2831
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Photoreceptor Neuroprotection in RCS Rats via Low-Dose Intravitreal Sustained-Delivery of Fluocinolone Acetonide

Inna V. Glybina,1 Alexander Kennedy,1 Paul Ashton,2 Gary W. Abrams,1 and Raymond Iezzi1,3

1From the Wayne State University School of Medicine, Department of Ophthalmology, Kresge Eye Institute, Ligon Research Center of Vision, Detroit, Michigan; and 2pSivida Ltd., Boston, Massachusetts.

PURPOSE. To study the neuroprotective effects of intravitreal fluocinolone acetonide (FA) in Royal College of Surgeons (RCS) rats.

METHODS. Five-week-old RCS rats were divided into four groups: 0.5 µg/d FA–loaded intravitreal drug-delivery implant (IDDI); 0.2 µg/d FA–loaded IDDI; inactive IDDI; and nonsurgical control. Electroretinography (ERG) and intraocular pressure (IOP) measurements were performed before surgery and weekly thereafter. Thicknesses of the retinal outer (ONL) and inner (INL) nuclear layers were evaluated at 9 weeks of age. ED-1–labeled activated microglia were counted. Total microglial cell counts were made by using Iba-1 antibody labeling.

RESULTS. At 9 weeks, control groups demonstrated an 80% reduction in ERG amplitudes (P < 0.001 for both groups). FA-treated groups demonstrated no statistically significant attenuation of ERG amplitudes at the end of the study, compared with the initial ERGs. Intraocular pressure (IOP) remained normal in all groups. ONL thickness in FA 0.2 µg/d–treated eyes was 2.1 ± 0.5 times greater than in nonsurgical eyes (P < 0.001) and 3.4 ± 0.7 times greater than in inactive IDDI-treated eyes (P < 0.0001). In FA 0.5 µg/d–treated eyes, ONL thickness was 1.5 ± 0.1 times higher than in nonsurgical controls (P < 0.05) and 2.4 ± 0.4 times higher than in inactive IDDI-treated eyes (P < 0.01). INL thickness was not different among groups. FA-treated eyes demonstrated significantly fewer activated microglia (P < 0.001) and overall number of microglia in the photoreceptor and outer debris zone layers (P < 0.001), compared with control groups.

CONCLUSIONS. Chronic intravitreal infusion of FA is neuroprotective in RCS rats, preserves ONL morphology and ERG amplitudes and reduces retinal neuroinflammation. These findings may have a therapeutic role in human photoreceptor cell degenerations.






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