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Eduardo M. Normando, Li Guo, Shereen Nizari, Joana M. Galvao, M Francesca Cordeiro; OCT In Vivo Imaging for Quantification of Retinal Structural Changes in Parkinson’s Disease Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5005.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal nerve fibre layer (RNFL) thinning is increasingly recognized as a potential biomarker for neurodegeneration in Parkinson's disease. Compared to the brain, the retina is easily accessible using techniques such as optical coherence tomography (OCT) to examine retinal structure non-invasively. Rotenone is used as a treatment in rats to detect medicines to treat human Parkinson’s Disease (PD). The aim of this study is to delineate the natural history of changes in the retinal layers in rats treated with rotenone.This work was supported by a grant from GSK China.
Dark Agouti rats (n = 36) were injected daily with rotenone or vehicle control, as previously described. Animals were imaged in vivo using methods we have previously established. Measurements of RNFL, inner plexform layer (IPL), and inner nuclear layer (INL) thickness were acquired simultaneously using the OCT Spectralis (Heidelberg Engineering). Imaging was performed in vivo at baseline, 10, 20, 40 and 60 days after initial rotenone injection. Histology was used to validate imaging findings.
At 10 days, there was a significant increase in whole retinal thickness (p<0.05) in the central, superior, inferior, nasal and temporal sectors in rotenone animals compared to control. This increase persisted until 60 days, although not reaching significance. An increase in RNFL thickness in rotenone eyes was found to reach significance compared to control at 40 & 60 days (General, Sup Temp and Infero Nasal sectors, p<0.05). Furthermore, histological changes in the INL (dopamine and alpha-synuclein) correlated with the development of OCT changes in this layer. Finally, a reduction in dopaminergic (DA) neurons in the substantia nigra and striatal dopamine, confirmed the validity of the model.
Our results show that changes in the retina occur early in this model of Parkinson’s Disease. The changes in thickness suggest that retinal neurons other than just RGCs, such as bipolar, horizontal and amacrine cells may be also affected in the early stages of disease. Further work is needed to delineate the relationship of these events to each other & functional changes. However, these results highlight the advantages of using real time parameters with imaging tissue changes in the retina (OCT) in PD models - methodologies that due to their non-invasive nature, can be easily applied to the patient.This work was supported by a grant from GSK China.
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