Survey of Ophthalmology
Volume 45, Supplement 3 , Pages S277-S283, May 2001

Maintaining Mitochondrial Membrane Impermeability:

An Opportunity for New Therapy in Glaucoma?

  • William G Tatton, MD, PhD

      Affiliations

    • Departments of Ophthalmology, Mount Sinai School of Medicine, New York, NY, USA
    • Departments of Neurology, Mount Sinai School of Medicine, New York, NY, USA
    • Corresponding Author InformationReprint address: Dr. William G. Tatton, Department of Neurology, Annenberg 14-70, Mount Sinai Medical Center, One Gustave L. Levy Place, New York, New York 10029.
    • ,
  • Ruth M.E Chalmers-Redman, PhD

      Affiliations

    • Departments of Neurology, Mount Sinai School of Medicine, New York, NY, USA
    • ,
  • Ajay Sud

      Affiliations

    • The School of Pharmacy, University of London, London, England, UK
    • ,
  • Steven M Podos, MD

      Affiliations

    • Departments of Ophthalmology, Mount Sinai School of Medicine, New York, NY, USA
    • ,
  • Thomas W Mittag, PhD

      Affiliations

    • Departments of Ophthalmology, Mount Sinai School of Medicine, New York, NY, USA

Abstract 

Apoptosis may contribute to retinal ganglion cell loss in glaucoma and glaucoma models. Recent research has suggested that mitochondrially dependent apoptosis signaling may contribute to apoptosis in a rat model of glaucoma involving chronic increases in intraocular pressure. In some forms of apoptosis, mitochondrially dependent signaling involves increases in mitochondrial membrane permeability and the mitochondrial release of factors that signal for cell degradation. Opening of a multi-protein, mitochondrial megapore is one factor that contributes to the increased permeability and some anti-apoptotic proteins, particularly BCL-2 and BCL-XL, bind at the megapore and facilitate megapore closure and reduce increases in mitochondrial membrane permeability. Phosphorylated protein kinase B (Akt) serves as an integrator for cellular survival signals and facilitates the megapore actions of BCL-2 and BCL-XL, which could protect retinal ganglion cells against insults that induce apoptosis. Several anti-apoptotic agents are being evaluated for use in glaucoma, including brimonidine and propargylamines, which oppose mitochondrially dependent apoptosis through pathways involving phosphorylated Akt.

Keywords:  apoptosis, glaucoma, mitochondrial membrane permeability, retinal, ganglion cell loss

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PII: S0039-6257(01)00207-7

Survey of Ophthalmology
Volume 45, Supplement 3 , Pages S277-S283, May 2001

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