TY - JOUR
T1 - Retinal macroglia changes in a triple transgenic mouse model of Alzheimer's disease
AU - Edwards, Malia M.
AU - Rodríguez, José J.
AU - Gutierrez-Lanza, Raquel
AU - Yates, Joseph
AU - Verkhratsky, Alexei
AU - Lutty, Gerard A.
N1 - Funding Information:
This research was supported by funding from the Knights Templar Eye Foundation (ME), NEI/NIH EY009357 (GL) and EY01765 (Wilmer), RPB (Wilmer), and AHAF (GL). This study was also supported by an Alzheimer's Research Trust Programme Grant ( ART/PG2004A/1 ) to JJR and AV. Support from the Spanish Government , Plan Nacional de I+D+I 2008-2011 and ISCIII-Subdirección General de Evaluación y Fomento de la Investigación ( PI10/02738 ) co-financed by FEDER to JJR and AV and the Government of the Basque Country ( AE-2010-1-28 , AEGV10/16 , GV-2011111020 ) are also gratefully acknowledged. The authors also thank D. Scott McLeod for assistance with figure preparation.
PY - 2014/10
Y1 - 2014/10
N2 - The retinas of Alzheimer's disease (AD) patients and transgenic AD animal models display amyloid beta deposits and degeneration of ganglion cells. Little is known, however, about the glial changes in the AD retina. The present study used a triple transgenic mouse model (3xTG-AD), which carries mutated human amyloid precursor protein, tau, and presenilin 1 genes and closely mimics the human brain pathology, to investigate retinal glial changes in AD. AD cognitive symptoms are known to begin in the 3xTG-AD mice at four months of age but plaques and tangles are not seen until six to twelve months. Müller cells in 3xTG-AD animals were GFAP-positive, indicating activation, at the earliest time point investigated, nine months. Astrocyte activation was also suggested in the 3xTG-AD mice by an apparent increase in size and process number. Another glial marker, S100, was expressed by astrocytes in both the non-transgenic (NTG) controls and 3xTG-AD retinas. Labeling was predominantly nuclear in nine month non-transgenic (NTG) control mice but was also seen in the cytoplasm and processes at 18 months of age. Interestingly, the nuclear localization was not as prominent in the 3xTG-AD retina even at nine months with labeling observed in astrocyte processes. The diffusion of S100 suggests the possible secretion of this protein, as is seen in the brain, with age and, more profoundly, associated with AD. Several dense, abnormally shaped, opaque structures were noted in all 3xTG-AD mice investigated. These structures, which were enveloped by GFAP and S100-positive astrocytes and Müller cells, were positive for amyloid beta, suggesting that they are amyloid plaques. Staining control retinas with amyloid showed similar structures in 30% of NTG animals but these were fewer in number and not associated with glial activation. The results herein indicate retinal glia activation in the 3xTG-AD mouse retina.
AB - The retinas of Alzheimer's disease (AD) patients and transgenic AD animal models display amyloid beta deposits and degeneration of ganglion cells. Little is known, however, about the glial changes in the AD retina. The present study used a triple transgenic mouse model (3xTG-AD), which carries mutated human amyloid precursor protein, tau, and presenilin 1 genes and closely mimics the human brain pathology, to investigate retinal glial changes in AD. AD cognitive symptoms are known to begin in the 3xTG-AD mice at four months of age but plaques and tangles are not seen until six to twelve months. Müller cells in 3xTG-AD animals were GFAP-positive, indicating activation, at the earliest time point investigated, nine months. Astrocyte activation was also suggested in the 3xTG-AD mice by an apparent increase in size and process number. Another glial marker, S100, was expressed by astrocytes in both the non-transgenic (NTG) controls and 3xTG-AD retinas. Labeling was predominantly nuclear in nine month non-transgenic (NTG) control mice but was also seen in the cytoplasm and processes at 18 months of age. Interestingly, the nuclear localization was not as prominent in the 3xTG-AD retina even at nine months with labeling observed in astrocyte processes. The diffusion of S100 suggests the possible secretion of this protein, as is seen in the brain, with age and, more profoundly, associated with AD. Several dense, abnormally shaped, opaque structures were noted in all 3xTG-AD mice investigated. These structures, which were enveloped by GFAP and S100-positive astrocytes and Müller cells, were positive for amyloid beta, suggesting that they are amyloid plaques. Staining control retinas with amyloid showed similar structures in 30% of NTG animals but these were fewer in number and not associated with glial activation. The results herein indicate retinal glia activation in the 3xTG-AD mouse retina.
KW - Alzheimer's disease
KW - Astrogliosis
KW - GFAP
KW - Müller cells
KW - Retina
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U2 - 10.1016/j.exer.2014.08.006
DO - 10.1016/j.exer.2014.08.006
M3 - Article
C2 - 25149907
AN - SCOPUS:84907316362
VL - 127
SP - 252
EP - 260
JO - Experimental Eye Research
JF - Experimental Eye Research
SN - 0014-4835
ER -