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 whole-mount preparations or sections of retinas from young adult or aged male Wistar rats.


RESULTS
Aged rats showed a significant impairment in short-term memory compared with young adults. Deterioration of blood-retinal barrier function in aged rats was evidenced by leakage of intravascular 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.


CONCLUSIONS
Breakdown of the blood-retinal barrier, MHC class II expression, microglial activation, and trafficking of activated T cells are associated with physiological aging. Such changes in the CNS may contribute to the pathogenesis of age-related cognitive decline.
Chan-Ling
Tailoi
T
Department of Anatomy, Bosch Institute, University of Sydney, Sydney, Australia. tailoi@anatomy.usyd.edu.au
Hughes
Suzanne
S
Baxter
Louise
L
Rosinova
Emelia
E
McGregor
Iain
I
Morcos
Yvette
Y
van Nieuwenhuyzen
Petra
P
Hu
Ping
P
D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000906:Antibodies; D001812:Blood-Brain Barrier / Q000276:immunology* / Q000473:pathology; D003072:Cognition Disorders / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D053331:Ectodysplasins / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006735:Horseradish Peroxidase; D007202:Indicators and Reagents; D007211:Indoles; D007249:Inflammation / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008833:Microcirculation / Q000276:immunology; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D062793:Occludin; D009942:Organometallic Compounds; D021381:Protein Transport / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D012171:Retinal Vessels / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019108:Tight Junctions / Q000502:physiology
D000906:Antibodies; D053331:Ectodysplasins; D000949:Histocompatibility Antigens Class II; D007202:Indicators and Reagents; D007211:Indoles; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D009942:Organometallic Compounds; C015445:copper phthalocyanine; D006735:Horseradish Peroxidase