PMID- 21633715
OWN - NLM
STAT- MEDLINE
DCOM- 20110926
LR  - 20211020
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 17
DP  - 2011
TI  - Age-related alterations in retinal neurovascular and inflammatory transcripts.
PG  - 1261-74
AB  - PURPOSE: Vision loss is one of the most common complications of aging, even in 
      individuals with no diagnosed ocular disease. Increasing age induces structural 
      alterations and functional impairments in retinal neurons and microvasculature 
      linked to the activation of proinflammatory signaling pathways. Commonalities 
      between the effects of aging and those observed with diabetes, including visual 
      impairment, vascular dysfunction, and increased inflammatory response, have led 
      to the hypothesis that diabetes-associated pathologies reflect an "advanced 
      aging" phenotype. The goal of this study was to investigate the effects of aging 
      on retinal mRNA expression of neurovascular and inflammatory transcripts 
      previously demonstrated to be regulated with diabetes. METHODS: The relative 
      expression of 36 genes of interest previously identified as consistently 
      regulated with diabetes was assessed in retinas of Young (3 month), Adult (12 
      month), and Aged (26 month) Fischer 344 x Brown Norway (F1) hybrid rats using 
      quantitative PCR. Serum samples obtained at sacrifice were assayed to determine 
      serum glucose levels. RESULTS: Eleven inflammation- and microvascular-related 
      genes previously demonstrated to be upregulated in young diabetic rats 
      (complement component 1 s subcomponent [C1s], chitinase 3-like 1 [Chi3L1], 
      endothelin 2 [Edn2], guanylate nucleotide binding protein 2 [Gbp2], glial 
      fibrillary acidic protein [Gfap], intracellular adhesion molecule 1 [Icam1], 
      janus kinase 3 [Jak3], lipopolysaccharide-induced TNF factor [Litaf], complement 
      1-inhibitor [Serping1], signal transducer and activator of transcription 3 
      [Stat3], tumor necrosis factor receptor subfamily member 12a [Tnfrsf12a]) 
      demonstrated progressively increasing retinal expression in aged normoglycemic 
      rats. Additionally, two neuronal function-related genes (glutamate receptor 
      ionotropic NMDA 2A [Grin2a] and polycomb group ring finger 1 [Pcgf1]) and one 
      inflammation-related gene (pigment epithelium-derived growth factor [Pedf]) 
      displayed patterns of expression dissimilar to that previously demonstrated with 
      diabetes. CONCLUSIONS: The commonalities in retinal age-related and 
      diabetes-induced molecular alterations provide support for the hypothesis that 
      diabetes and aging engage some common para-inflammatory processes. However, these 
      results also demonstrate that while the retinal genomic response to diabetes and 
      aging share commonalities, they are not superimposable phenotypes. The observed 
      changes in retinal gene expression provide further evidence of retinal 
      alterations in neurovascular and inflammatory processes across the adult rat 
      lifespan; this is indicative of para-inflammation that may contribute to the 
      functional impairments that occur with advanced age. The data also suggest the 
      potential for an additive effect of aging and diabetes in the development of 
      diabetic complications.
CI  - (c) 2011 Molecular Vision
FAU - Van Kirk, Colleen A
AU  - Van Kirk CA
AD  - Department of Pharmacology, Penn State College of Medicine, University Drive, 
      Hershey, PA 17033, USA.
FAU - VanGuilder, Heather D
AU  - VanGuilder HD
FAU - Young, Megan
AU  - Young M
FAU - Farley, Julie A
AU  - Farley JA
FAU - Sonntag, William E
AU  - Sonntag WE
FAU - Freeman, Willard M
AU  - Freeman WM
LA  - eng
GR  - P01 AG011370/AG/NIA NIH HHS/United States
GR  - R01 AG026607/AG/NIA NIH HHS/United States
GR  - P01AG11370/AG/NIA NIH HHS/United States
GR  - R01AG026607/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110507
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (Blood Glucose)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Aging/*metabolism
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Hybridization, Genetic
MH  - Inflammation/genetics
MH  - Male
MH  - Microcirculation/genetics
MH  - Neurons/physiology
MH  - RNA, Messenger/*metabolism
MH  - Rats
MH  - Rats, Inbred BN
MH  - Rats, Inbred F344
MH  - Retina/*metabolism
MH  - Retinal Vessels/physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC3103744
EDAT- 2011/06/03 06:00
MHDA- 2011/09/29 06:00
PMCR- 2011/01/01
CRDT- 2011/06/03 06:00
PHST- 2010/09/11 00:00 [received]
PHST- 2011/05/03 00:00 [accepted]
PHST- 2011/06/03 06:00 [entrez]
PHST- 2011/06/03 06:00 [pubmed]
PHST- 2011/09/29 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - 142 [pii]
AID - 2010MOLVIS0391 [pii]
PST - ppublish
SO  - Mol Vis. 2011;17:1261-74. Epub 2011 May 7.