Age-related alterations in retinal neurovascular and inflammatory transcripts

Collen A. van Hirk, Heather D. VanGuilder, Megan Marie Young, Julie A. Farley, William E. Sonntag, Willard M. Freeman

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1261-1274
Number of pages14
JournalMolecular vision
Volume17
StatePublished - May 30 2011

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Complement C1
Complement Inactivating Agents
Inflammation
Janus Kinase 3
Endothelin-2
Genes
Retinal Neurons
Phenotype
Gene Expression
STAT3 Transcription Factor
Chitinases
Eye Diseases
Tumor Necrosis Factor Receptors
Glial Fibrillary Acidic Protein
Vision Disorders
Glutamate Receptors
Diabetes Complications
Norway
Microvessels
Serum

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

van Hirk, C. A., VanGuilder, H. D., Young, M. M., Farley, J. A., Sonntag, W. E., & Freeman, W. M. (2011). Age-related alterations in retinal neurovascular and inflammatory transcripts. Molecular vision, 17, 1261-1274.
van Hirk, Collen A. ; VanGuilder, Heather D. ; Young, Megan Marie ; Farley, Julie A. ; Sonntag, William E. ; Freeman, Willard M. / Age-related alterations in retinal neurovascular and inflammatory transcripts. In: Molecular vision. 2011 ; Vol. 17. pp. 1261-1274.
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abstract = "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.",
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van Hirk, CA, VanGuilder, HD, Young, MM, Farley, JA, Sonntag, WE & Freeman, WM 2011, 'Age-related alterations in retinal neurovascular and inflammatory transcripts', Molecular vision, vol. 17, pp. 1261-1274.

Age-related alterations in retinal neurovascular and inflammatory transcripts. / van Hirk, Collen A.; VanGuilder, Heather D.; Young, Megan Marie; Farley, Julie A.; Sonntag, William E.; Freeman, Willard M.

In: Molecular vision, Vol. 17, 30.05.2011, p. 1261-1274.

Research output: Contribution to journalArticle

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T1 - Age-related alterations in retinal neurovascular and inflammatory transcripts

AU - van Hirk, Collen A.

AU - VanGuilder, Heather D.

AU - Young, Megan Marie

AU - Farley, Julie A.

AU - Sonntag, William E.

AU - Freeman, Willard M.

PY - 2011/5/30

Y1 - 2011/5/30

N2 - 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.

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van Hirk CA, VanGuilder HD, Young MM, Farley JA, Sonntag WE, Freeman WM. Age-related alterations in retinal neurovascular and inflammatory transcripts. Molecular vision. 2011 May 30;17:1261-1274.