title: A decrease in retinal progenitor cells is associated with early features of diabetic retinopathy in a model that combines diabetes and hypertension.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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
authors.forename: Jacqueline Mendonça
authors.initials: JM
authors.lastname: Lopes de Faria
authors.forename: Kamila Cristina
authors.initials: KC
authors.lastname: Silva
authors.forename: Patrícia Aline
authors.initials: PA
authors.lastname: Boer
authors.forename: Tiago Correa
authors.initials: TC
authors.lastname: Cavalcanti
authors.forename: Mariana Aparecida Brunini
authors.initials: MA
authors.lastname: Rosales
authors.forename: Ana Luiza
authors.initials: AL
authors.lastname: Ferrari
authors.forename: José Butori
authors.initials: JB
authors.lastname: Lopes de Faria
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D001813:Blood-Retinal Barrier / Q000503:physiopathology; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology; D002452:Cell Count; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012160:Retina / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D042461:Vascular Endothelial Growth Factor A; D050760:Cyclin-Dependent Kinase Inhibitor p27; D001973:Bromodeoxyuridine