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Interrelationship between activation of matrix metalloproteinases and mitochondrial dysfunction in the development of

Julia M Santos1, Shikha Tewari, Jonathan Y Lin

  • 1Kresge Eye Institute, Wayne State University, Detroit, MI 48201, United States.

Biochemical and Biophysical Research Communications
|July 30, 2013
PubMed

Insights

Diabetic retinopathy involves matrix metalloproteinases (MMP-9 and MMP-2) damaging retinal mitochondria early. Targeting these MMPs in early diabetes may prevent vision loss.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Diabetology

Background:

  • Mitochondria dysfunction is key in retinal cell apoptosis.
  • Diabetes mellitus activates matrix metalloproteinases (MMPs), leading to retinal cell damage and apoptosis.

Purpose of the Study:

  • To investigate the temporal relationship between matrix metalloproteinase (MMP) activation and mitochondrial damage in diabetic retinopathy.
  • To understand the early events in the pathogenesis of diabetic retinopathy.

Main Methods:

  • Investigated the time course of cytosolic MMP-9 and MMP-2 activation in high-glucose-incubated retinal endothelial cells.
  • Correlated MMP activation with mitochondrial accumulation and damage in vitro.
  • Confirmed findings in retinas from streptozotocin-induced diabetic rats over time.

Main Results:

  • Cytosolic MMP-9 and MMP-2 activation is an early event in diabetes.
  • Activated MMPs accumulate in mitochondria, causing dysfunction and DNA damage.
  • This initiates a cycle of reactive oxygen species, contributing to diabetic retinopathy.

Conclusions:

  • Early activation and mitochondrial accumulation of MMP-9 and MMP-2 are critical in diabetic retinopathy development.
  • Modulating gelatinase MMPs pharmacologically early in diabetes may prevent disease progression.
  • This offers a potential therapeutic strategy for diabetic retinopathy.
Keywords:
DiabetesMatrix metalloproteinaseMitochondriaRetinopathy

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