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A decrease in retinal progenitor cells is associated with early features of diabetic retinopathy in a model that combines diabetes and hypertension.
Mol Vis. 2008 Sep 11; 14:1680-91.MV

Abstract

PURPOSE

Hyperglycemia and hypertension contribute to the development of diabetic retinopathy, and this may involve alterations in the normal retinal cell cycle. In this work, we examined the influence of diabetes and hypertension on retinal cell replication in vivo and the relationship between these changes and several early markers of diabetic retinopathy.

METHODS

Diabetes was induced with streptozotocin in 4- and 12-week-old spontaneously hypertensive rats (SHR) and their Wistar Kyoto (WKY) controls. The rats were killed 15 days later. Retinal cells stained with bromodeoxyuridine (BrdU) were seen in rats of both ages.

RESULTS

In 12-week-old rats, the number of BrdU-positive retinal cells was higher in SHR than in WKY rats. After 15 days of diabetes mellitus, there was a marked reduction in cell replication only in diabetic SHR (p=0.007). The BrdU-positive cells expressed neural, glial, or vascular progenitor markers. There was greater expression of p27(Kip1) in the ganglion cell layer of both diabetic groups (p=0.05), whereas in the inner nuclear layer there was enhanced expression only in diabetic SHR (p=0.02). There was a marked increase in the retinal expression of fibronectin (p=0.04) and vascular endothelial growth factor (p=0.02) in diabetic SHR that was accompanied by blood-retinal barrier breakdown (p=0.01).

DISCUSSION

Concomitant diabetes and hypertension attenuated the proliferation of retinal cells, and it is associated with an increase in p27(Kip1) expression, fibronectin accumulation, and blood-retinal barrier breakdown. The replicative retinal cells displayed characteristics of progenitor cells.

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Authors+Show Affiliations

Lopes de Faria JM
Department of Internal Medicine, Faculty of Medical Sciences, Renal Pathophysiology Laboratory, Investigation in Diabetes Complications, State University of Campinas, Campinas, São Paulo, Brazil. jmlfaria@fcm.unicamp.br
Silva KC
No affiliation info available
Boer PA
No affiliation info available
Cavalcanti TC
No affiliation info available
Rosales MA
No affiliation info available
Ferrari AL
No affiliation info available
Lopes de Faria JB
No affiliation info available

MeSH

AgingAnimalsBlood-Retinal BarrierBlotting, WesternBromodeoxyuridineCapillary PermeabilityCell CountCyclin-Dependent Kinase Inhibitor p27Diabetic RetinopathyDisease Models, AnimalFluorescent Antibody TechniqueGlial Fibrillary Acidic ProteinHypertensionIn Situ Nick-End LabelingRatsRats, Inbred SHRRats, Inbred WKYRetinaStem CellsTime FactorsVascular Endothelial Growth Factor A

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18806882

Citation

Lopes de Faria, Jacqueline Mendonça, et al. "A Decrease in Retinal Progenitor Cells Is Associated With Early Features of Diabetic Retinopathy in a Model That Combines Diabetes and Hypertension." Molecular Vision, vol. 14, 2008, pp. 1680-91.
Lopes de Faria JM, Silva KC, Boer PA, et al. A decrease in retinal progenitor cells is associated with early features of diabetic retinopathy in a model that combines diabetes and hypertension. Mol Vis. 2008;14:1680-91.
Lopes de Faria, J. M., Silva, K. C., Boer, P. A., Cavalcanti, T. C., Rosales, M. A., Ferrari, A. L., & Lopes de Faria, J. B. (2008). A decrease in retinal progenitor cells is associated with early features of diabetic retinopathy in a model that combines diabetes and hypertension. Molecular Vision, 14, 1680-91.
Lopes de Faria JM, et al. A Decrease in Retinal Progenitor Cells Is Associated With Early Features of Diabetic Retinopathy in a Model That Combines Diabetes and Hypertension. Mol Vis. 2008 Sep 11;14:1680-91. PubMed PMID: 18806882.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A decrease in retinal progenitor cells is associated with early features of diabetic retinopathy in a model that combines diabetes and hypertension. AU - Lopes de Faria,Jacqueline Mendonça, AU - Silva,Kamila Cristina, AU - Boer,Patrícia Aline, AU - Cavalcanti,Tiago Correa, AU - Rosales,Mariana Aparecida Brunini, AU - Ferrari,Ana Luiza, AU - Lopes de Faria,José Butori, Y1 - 2008/09/11/ PY - 2008/01/30/received PY - 2008/08/25/accepted PY - 2008/9/23/pubmed PY - 2008/11/15/medline PY - 2008/9/23/entrez SP - 1680 EP - 91 JF - Molecular vision JO - Mol Vis VL - 14 N2 - PURPOSE: Hyperglycemia and hypertension contribute to the development of diabetic retinopathy, and this may involve alterations in the normal retinal cell cycle. In this work, we examined the influence of diabetes and hypertension on retinal cell replication in vivo and the relationship between these changes and several early markers of diabetic retinopathy. METHODS: Diabetes was induced with streptozotocin in 4- and 12-week-old spontaneously hypertensive rats (SHR) and their Wistar Kyoto (WKY) controls. The rats were killed 15 days later. Retinal cells stained with bromodeoxyuridine (BrdU) were seen in rats of both ages. RESULTS: In 12-week-old rats, the number of BrdU-positive retinal cells was higher in SHR than in WKY rats. After 15 days of diabetes mellitus, there was a marked reduction in cell replication only in diabetic SHR (p=0.007). The BrdU-positive cells expressed neural, glial, or vascular progenitor markers. There was greater expression of p27(Kip1) in the ganglion cell layer of both diabetic groups (p=0.05), whereas in the inner nuclear layer there was enhanced expression only in diabetic SHR (p=0.02). There was a marked increase in the retinal expression of fibronectin (p=0.04) and vascular endothelial growth factor (p=0.02) in diabetic SHR that was accompanied by blood-retinal barrier breakdown (p=0.01). DISCUSSION: Concomitant diabetes and hypertension attenuated the proliferation of retinal cells, and it is associated with an increase in p27(Kip1) expression, fibronectin accumulation, and blood-retinal barrier breakdown. The replicative retinal cells displayed characteristics of progenitor cells. SN - 1090-0535 UR - https://www.unboundmedicine.com/medline/citation/18806882/A_decrease_in_retinal_progenitor_cells_is_associated_with_early_features_of_diabetic_retinopathy_in_a_model_that_combines_diabetes_and_hypertension_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18806882/ DB - PRIME DP - Unbound Medicine ER -