Secretory Autophagy is Increased in 5xfad Mice

AbstractPurpose: Chronic oxidative stress, disturbed proteostasis and increased protein aggregation are key hallmarks in Alzheimer's disease and age‐related macular degeneration pathology. In this study, we assessed the protein aggregation and secretory autophagy related biomarker changes in 5xFAD mice model expressing abundant levels of human beta‐amyloid (Aβ42).Methods: The eyes of 6‐ and 12‐month‐old WT (n = 5) and 5xFAD (n = 5) were examined by immunomicroscopy. The paraffin sections were immunostained with the key regulators of secretory autophagy HMGB1, Aβ42, IL‐1β, and ferritin as well as protein aggregation markers ubiquitin protein and SQSTM1/p62.Results: Immunohistochemistry analysis revealed that ubiquitin protein conjugates and Aβ42 were increased in 6 and 12 months old 5xFAD mice. SQSTM1/p62 was decreased in 12 months old 5xFAD mice. In 12‐month‐old time point, they located basolateral side of the retinal pigment epithelial (RPE) cells but also in extracellular space. Concurrently, secretory autophagy markers were elevated in the RPE and extracellular space between RPE and Bruch's membrane.Conclusions: Secretary autophagy may be a novel regulator in drusen biogenesis. 5xFAD mouse is a good model to study protein aggregation and secretory autophagy mechanism in response to degenerative retina processes.