Nanoparticle-delivered biosensor for reactive oxygen species in diabetes

Tarl W. Prow, Imran Bhutto, Rhonda Grebe, Koichi Uno, Carol Merges, D. Scott Mcleod, Gerard Anthony Lutty

Research output: Contribution to journalArticle

Abstract

The cell's own antioxidant response element (ARE) can be used to evaluate the complications of diabetes mellitus. The hypothesis that a synthetic ARE could be used as a genetic switch, or biosensor, to turn on and off therapeutic genes is tested herein. Mitochondrial oxidative stress (MOS) has been hypothesized as one of the earliest insults in diabetes. Fluorescent probes used to monitor MOS revealed that the addition of glucose at physiological levels to cultures of endothelial cells was able to induce MOS above normal levels and in a dose-dependant manner. Additional data showed that increased glucose levels activated the ARE-GFP in a dose-dependant manner. These data support the hypothesis that the induction of MOS is more sensitive to hyperglycemia than the induction of the ARE. Delivery of an ARE-GFP construct with nanoparticles to the eye was successful using sub-retinal injection. This ARE-GFP/nanoparticle construct was functional and reported the activation of the ARE in diabetic rat retinal pigment epithelium (RPE). These data support the use of nanoparticle-delivered biosensors for monitoring the oxidative status of tissues in vivo.

Original languageEnglish (US)
Pages (from-to)478-485
Number of pages8
JournalVision Research
Volume48
Issue number3
DOIs
StatePublished - Feb 2008

Fingerprint

Antioxidant Response Elements
Biosensing Techniques
Nanoparticles
Reactive Oxygen Species
Oxidative Stress
Glucose
Retinal Pigment Epithelium
Diabetes Complications
Fluorescent Dyes
Hyperglycemia
Endothelial Cells
Injections

Keywords

  • Antioxidant response element
  • Biosensor
  • Diabetes
  • Gene delivery
  • Hyperglycemia
  • Nanoparticle

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Nanoparticle-delivered biosensor for reactive oxygen species in diabetes. / Prow, Tarl W.; Bhutto, Imran; Grebe, Rhonda; Uno, Koichi; Merges, Carol; Mcleod, D. Scott; Lutty, Gerard Anthony.

In: Vision Research, Vol. 48, No. 3, 02.2008, p. 478-485.

Research output: Contribution to journalArticle

Prow, Tarl W. ; Bhutto, Imran ; Grebe, Rhonda ; Uno, Koichi ; Merges, Carol ; Mcleod, D. Scott ; Lutty, Gerard Anthony. / Nanoparticle-delivered biosensor for reactive oxygen species in diabetes. In: Vision Research. 2008 ; Vol. 48, No. 3. pp. 478-485.
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