Mitochondrial dysfunction in glaucoma: understanding genetic influences

Mitochondrion. 2012 Mar;12(2):202-12. doi: 10.1016/j.mito.2011.11.004. Epub 2011 Nov 28.


Glaucoma is the leading cause of irreversible blindness worldwide. This review aims to provide a greater understanding of the complex genetic influences that may lead to mitochondrial dysfunction and increase susceptibility to retinal ganglion cell (RGC) loss in primary open angle glaucoma (POAG), and thus elucidate potentially important pathophysiological pathways amenable to therapeutic intervention. Emerging evidence from genome wide association and other genetic studies suggests that changes in the mitochondrial DNA (mtDNA) and in nuclear DNA genes that encode mitochondrial proteins may influence mitochondrial structure and function and, therefore, contribute to the pathogenesis of POAG. We propose that a variety of genes (OPA1, MFN1, MFN2, CYP1B1, PARL, SOD2, SRBD1, GST, NOS3, TNFa and TP53) may each confer a background susceptibility to POAG in different populations having one common link: mitochondrial dysfunction. The relationship between polymorphisms in these genes and increasing risk for POAG is presented and the limitations of the available current knowledge are discussed.

Publication types

  • Review

MeSH terms

  • Genes, Mitochondrial
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Glaucoma, Open-Angle / congenital
  • Glaucoma, Open-Angle / genetics*
  • Glaucoma, Open-Angle / physiopathology*
  • Humans
  • Mitochondria / pathology*
  • Mitochondria / physiology*
  • Mitochondrial Proteins / genetics


  • Mitochondrial Proteins