Details

Autor(en) / Beteiligte

• de Sousa, Luís Miguel Antunes

Titel

Elucidating the Role of Synucleins in Retinal Neurodegeneration in Parkinson’s Disease Diabetes and Ageing

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2018

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Retinal neurodegeneration occurs in Parkinson’s disease (PD),Diabetes Mellitus(DM) and with ageing. Aside from the thinning of the ganglion cell layer (GCL) and inner nuclear layer (INL) in the retina, the dopaminergic system, crucial for global retina function, is also affected in these three circumstances.Diabetic and ageing cellular environments share several cellular environments known to be present in PD, whose pathogenicity in the brain is associated with the synuclein family, which is composed by alpha-synuclein (aSyn), beta-synuclein (bSyn)and gamma-synuclein (gSyn). As synucleins are also present in the retina, they may also play neurotoxic roles by impairing synaptic activity and cell survival.Therefore, this study aimed to characterize the synucleins distribution profile in the retina by immunohistochemistry, and their protein levels through western blot, in the MitoPark PD mouse model, in DM animal models (high-fat diet (HFD) mouse and Zucker diabetic fatty (ZDF) rat), and in naturally ageing and accelerated ageing rats (D-Galactose treatment). This characterization was used to test a correlation with retinal neurodegeneration, by evaluating protein levels by western blot of synaptic and cell survival markers as readouts.The results show that MitoPark mice retina have increased bSyn protein levels and decreased Synaptophys in levels. Naturally ageing rats only present, of all the parameters tested, reduced thickness of retinal layers and cell density in the GCL, whereas the D-Galactose rats exhibit increased GCL cell density. D-Galactose rats also show a decreased aSyn-bSyn colocalization in the GCL and reduced protein levels of NF-κB.HFD mice do not show any alteration on the tested parameters, which contrasts with the observation of increased gSyn-positive cell bodies in the GCL of ZDF rats.Altogether, this work enlightened synucleins retinal distribution in all these animal models and global results point to subtle changes, which may correlate with neurodegeneration.