Increased oxidative and nitrative stress accelerates aging of the retinal vasculature in the diabetic retina

Folami Lamoke Powell, Sean Shaw, Jianghe Yuan, Sudha Ananth, Michael B Duncan, Pamela Moore Martin, Manuela Bartoli

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27 Citations (Scopus)

Abstract

Hyperglycemia-induced retinal oxidative and nitrative stress can accelerate vascular cell aging, which may lead to vascular dysfunction as seen in diabetes. There is no information on whether this may contribute to the progression of diabetic retinopathy (DR). In this study, we have assessed the occurrence of senescence-associated markers in retinas of streptozotocin- induced diabetic rats at 8 and 12 weeks of hyperglycemia as compared to normoglycemic aging (12 and 14 months) and adult (4.5 months) rat retinas. We have found that in the diabetic retinas there was an up-regulation of senescence-associated markers SA-β-Gal, p16INK4a and miR34a, which correlated with decreased expression of SIRT1, a target of miR34a. Expression of senescence-associated factors primarily found in retinal microvasculature of diabetic rats exceeded levels measured in adult and aging rat retinas. In aging rats, retinal expression of senescence associated-factors was mainly localized at the level of the retinal pigmented epithelium and only minimally in the retinal microvasculature. The expression of oxidative/nitrative stress markers such as 4-hydroxynonenal and nitrotyrosine was more pronounced in the retinal vasculature of diabetic rats as compared to normoglycemic aging and adult rat retinas. Treatments of STZ-rats with the anti-nitrating drug FeTPPS (10mg/Kg/day) significantly reduced the appearance of senescence markers in the retinal microvasculature. Our results demonstrate that hyperglycemia accelerates retinal microvascular cell aging whereas physiological aging affects primarily cells of the retinal pigmented epithelium. In conclusion, hyperglycemia-induced retinal vessel dysfunction and DR progression involve vascular cell senescence due to increased oxidative/nitrative stress.

Original languageEnglish (US)
Article numbere0139664
JournalPLoS One
Volume10
Issue number10
DOIs
StatePublished - Oct 14 2015

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retina
Retina
Rats
Oxidative Stress
Aging of materials
rats
hyperglycemia
Hyperglycemia
Cell Aging
Microvessels
blood vessels
diabetic retinopathy
Blood Vessels
Oxidative stress
Diabetic Retinopathy
oxidative stress
epithelium
Epithelium
Retinal Vessels
streptozotocin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Increased oxidative and nitrative stress accelerates aging of the retinal vasculature in the diabetic retina. / Powell, Folami Lamoke; Shaw, Sean; Yuan, Jianghe; Ananth, Sudha; Duncan, Michael B; Martin, Pamela Moore; Bartoli, Manuela.

In: PLoS One, Vol. 10, No. 10, e0139664, 14.10.2015.

Research output: Contribution to journalArticle

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