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 Abrams 1,
and
Raymond Iezzi 3*
1 Ophthalmology, Kresge Eye Institute, Detroit, Michigan, United States
2 pSivida, Watertown, Massachusetts, United States
3 Ophthalmology, Kresge Eye Institute, 4717 St. Antoine, Detroit, Michigan, 48084, United States
* To whom correspondence should be addressed. E-mail: riezzi{at}med.wayne.edu.
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Abstract |
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Purpose: To study neuroprotective effects of intravitreal fluocinolone acetonide (FA) in Royal College of Surgeons (RCS) rats.
Methods: Five-week RCS rats 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 weekly post-operatively. At nine-weeks of age, thicknesses of retinal outer (ONL) and inner (INL) nuclear layers were evaluated. ED-1-labeled activated microglia were counted. Total microglial cell counts were made using Iba-1 antibody labeling.
Results: At nine 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, as compared to the initial ERGs. Intraocular pressure (IOP) remained normal in all groups. ONL thickness in FA 0.2µg/day-treated eyes was 2.1±0.5 times greater than in unoperated eyes (p<0.001) and 3.4±0.7 times greater than in inactive IDDI-treated eyes (p<0.0001). In FA 0.5µg/day-treated eyes, ONL thickness was 1.5±0.1 times higher than in unoperated 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 to control groups.
Conclusion: 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.
Key Words:
retinitis pigmentosa, corticosteroids, drug delivery, anti-inflammatory agents, retinal degeneration, photoreceptor dystrophy
