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Eduardo M Normando, Ben Davis, Shereen Nizari, Lisa Turner, Giulia Malaguarnera, Li Guo, M Francesca Cordeiro; Neuroprotective Effect of Rosiglitazone on Retinal Changes in a Rat Model of Parkinson’s Disease . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4362.
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© ARVO (1962-2015); The Authors (2016-present)
Currently there is an unmet need for early diagnosis and neuroprotective strategies in Parkinson’s Disease (PD). Recently, several studies have also reported that Rosiglitazone (RSG) may be of therapeutic benefit in PD. The aim of this study is to determine whether retinal changes (apoptotic counts and retinal layer thickness) can be used as a biomarker to study effects of systemic treatment in experimental PD.
Dark Agouti rats (n = 24) were injected daily with rotenone (Rot) or vehicle control for 10 days. Animals were then either left untreated for another 10 days, or treated with daily RSG for 10 days. Retinal Ganglion Cells (RGCs) apoptosis was assessed using DARC and measurements of whole retina, Retinal Nerve Fiber Layer (RNFL), Inner Nuclear Layer (INL) and photoreceptor layer (IS/OS) thickness were obtained simultaneously using SD-OCT. Imaging was performed in vivo at baseline and at 20 days after initial Rot administration. Histology was used to validate in-vivo findings.
Animals treated with Rot revealed a significant increase in RGCs apoptosis after daily Rot administration (68.4 ± 4.6 vs. 33.4 ± 11.5; p<0.001). OCT imaging showed increase in whole retinal thickness (103% ± 2.3% vs. 97.9% ± 1.1%; p<0.01), RNFL (109.5% ± 2.95% vs. 97.4% ± 0.85%; p<0.01), ONL (102.86% ± 1.8% vs. 98.2% ± 0.76%; p<0.05) and IS/OS (106.43% ± 1.3% vs. 99% ± 1.3%; p<0.001) in Rot animals compared to vehicle control. A significant reduction in RGC apoptosis was seen in RSG treated animals (20.7 ± 1.3 spots vs. 68.4 ± 4.6 spots; p<0.001) compared to Rot. A preservation of whole retina (100.6% ± 0.3% vs. 103% ± 2.3%; p<0.01), RNFL (100.6% ± 0.2% vs. 109.5% ± 2.95%; p<0.001) and IS/OS (100.4% ± 0.6% vs. 106.43% ± 1.3%; p<0.001) thickness was also seen in RSG compared to Rot treated animals.
We have shown that RSG is neuroprotective in experimental PD, as shown using retinal imaging with DARC and OCT. This novel finding highlights the potential use of the eye as a window onto the brain, using non-invasive and accessible retinal imaging technology, with important implications for translation to the clinic, where better end point in PD are clearly needed.
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