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Eduardo Maria Normando, Ben Davis, Jonathan Brenton, Li Guo, M Francesca Cordeiro; Retinal Neuroprotective Effect of a Liposomal Formulation of Rosiglitazone in a Rat Model of Parkinson’s Disease. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4406.
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© ARVO (1962-2015); The Authors (2016-present)
In a previous study we have characterised, in-vivo, retinal changes (apoptotic counts and retinal layer thickness) in a well-established rotenone model of Parkinson’s Disease (PD). Furthermore, we have demonstrated the retinal neuroprotective effect of daily systemic Rosiglitazone (RSG) in the same model. The aim of this study is to determine the therapeutic efficacy of a novel single-administration of sustained release Rosiglitazone liposome formulations in the rotenone model of PD.
A liposomal formulation of RSG was prepeared using a method previously described (Davis, 2014 and 2015). Dark Agouti rats (n=15) were injected daily with rotenone for 10 days. Animals were either then left untreated for another 10 days (Rot, n=5), treated with daily RSG for 10 days (RSG, n=5) or given a single dose of liposome encapsulated RSG (RLP, n=5). Retinal Ganglion Cells (RGCs) apoptosis was assessed using DARC and measurements of whole retina, Retinal Nerve Fibre Layer (RNFL), Inner Nuclear Layer (INL) and photoreceptor layer (IS/OS) thickness were obtained using SD-OCT. Imaging was performed in vivo at baseline and at 20 days after initial Rotenone administration.
A significant reduction in RGC apoptosis was observed in RSG compared to Rot (p < 0.001). Likewise, a preservation of whole retina (p<0.01), RNFL (p<0.001) and IS/OS (p<0.001) thickness was also seen in RSG compared to Rot. A further significant reduction in RGC apoptosis was observed in RLP compared to Rot (p < 0.001). RLP reduced the level of RGCs apoptosis significantly more than RSG (p<0.0001). OCT structural analysis also confirmed preservation of whole retinal layers thickness in RLP compared to Rot (p<0.001) and RSG (p<0.05).
In the present study, a sustained release Rosiglitazone formulations was assessed. Rosiglitazone was significantly effective at reducing apoptosis after repeated daily administration. However, liposomal encapsulated Rosiglitazone given once only was demonstrated to offer a significant retinal neuroprotective effect in a rat model of PD when compared to daily administration of the free Rosiglitazone.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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