title: Age-related alterations in retinal neurovascular and inflammatory transcripts.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmacology, Penn State College of Medicine, University Drive, Hershey, PA 17033, USA.
authors.forename: Colleen A
authors.initials: CA
authors.lastname: Van Kirk
authors.forename: Heather D
authors.initials: HD
authors.lastname: VanGuilder
authors.forename: Megan
authors.initials: M
authors.lastname: Young
authors.forename: Julie A
authors.initials: JA
authors.lastname: Farley
authors.forename: William E
authors.initials: WE
authors.lastname: Sonntag
authors.forename: Willard M
authors.initials: WM
authors.lastname: Freeman
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D006824:Hybridization, Genetic; D007249:Inflammation / Q000235:genetics; D008297:Male; D008833:Microcirculation / Q000235:genetics; D009474:Neurons / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D012160:Retina / Q000378:metabolism*; D012171:Retinal Vessels / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose; D012333:RNA, Messenger