Aging-related changes in astrocytes in the rat retina: imbalance between cell proliferation and cell death reduces astrocyte availability.
The aim of this study was to investigate changes in astrocyte density, morphology, proliferation and apoptosis occurring in the central nervous system during physiological aging. Astrocytes in retinal whole-mount preparations from Wistar rats aged 3 (young adult) to 25 months (aged) were investigated qualitatively and quantitatively following immunofluorohistochemistry. Glial fibrillary acidic protein (GFAP), S100 and Pax2 were used to identify astrocytes, and blood vessels were localized using Griffonia simplicifolia isolectin B4. Cell proliferation was assessed by bromodeoxyuridine incorporation and cell death by TUNEL-labelling and immunolocalization of the apoptosis markers active caspase 3 and endonuclease G. The density and total number of parenchymal astrocytes in the retina increased between 3 and 9 months of age but decreased markedly between 9 and 12 months. Proliferation of astrocytes was detected at 3 months but virtually ceased beyond that age, whereas the proportion of astrocytes that were TUNEL positive and relative expression of active caspase 3 and endonuclease G increased progressively with aging. In addition, in aged retinas astrocytes exhibited gliosis-like morphology and loss of Pax2 reactivity. A small population of Pax2(+)/GFAP(-) cells was detected in both young adult and aged retinas. The reduction in the availability of astrocytes in aged retinas and other aging-related changes reported here may have a significant impact on the ability of astrocytes to maintain homeostasis and support neuronal function in old age.
Mansour
Hussein
H
School of Medical Sciences (Anatomy and Histology) and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia. tailoi@anatomy.usyd.edu.au
Chamberlain
Coral G
CG
Weible
Michael W
MW
Hughes
Suzanne
S
Chu
Yi
Y
Chan-Ling
Tailoi
T
D000375:Aging / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death; D049109:Cell Proliferation; D048430:Cell Shape; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology; D051762:PAX2 Transcription Factor / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D009418:S100 Proteins / Q000378:metabolism
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D051762:PAX2 Transcription Factor; D009418:S100 Proteins