Inflammation and breakdown of the blood-retinal barrier during "physiological aging" in the rat retina: A model for CNS aging

Objective: To examine the possible contribution of inflammation and breakdown of the blood-brain barrier in the central nervous system (CNS) of physiologically aged rats showing cognitive decline. Methods: Young (3- to 6-month-old) and aged (24- to 30-month-old) Wistar rats were assessed by the novel object recognition test. Vascular and inflammatory changes in the CNS were investigated in 71 71 7) whole-mount preparations or sections of retinas from young adult or aged male Wistar rats. Results: Aged rats showed a significant impairment short-term memory compared with young adults. Deterioration of blood-retinal barrier function in aged rats was evidenced by leakage of intravascular n tracer into the retinal parenchyma, and reduced immunoreactivity for the tight junctional protein, occludin. Immunohistochemistry revealed the presence of major histocompatibility complex (MHC) class II-positive resident microglia, activated T cells., and monocyte-like cells in the retinal parenchyma of aged rats only. Microglia positive for the ED1 antigen. indicative of phagocytic activity, were also observed in these retinas. Conclusion: Breakdown of the blood-retinal barrier, MHC class 11 expression, microglial activatio and trafficking, of activated T cells are associated with physiological aging. Such changes ill the CNS may contribute to the pathogenesis of age-related cognitive electric.