Related Experiment Video
Updated: Sep 10, 2026

Multi-parameter Measurement of the Permeability Transition Pore Opening in Isolated Mouse Heart Mitochondria
Published on: September 7, 2012
Cell-type-specific opening of the retinal ganglion cell mitochondrial permeability transition pore
Joshua P Vrabec1, Christopher J Lieven, Leonard A Levin
1University of Wisconsin Medical School, Department of Ophthalmology and Visual Sciences, Madison, Wisconsin 53792-4673, USA.
Purpose:
To study the role of the mitochondrial permeability transition pore (PTP) in apoptosis of axotomized retinal ganglion cells (RGCs) in vitro.
Methods:
Primary rat retinal cultures containing DiI-labeled RGCs were treated with pharmacological agents that modulate the PTP. Ratiometric imaging of the mitochondrial membrane potential (DeltaPsi(m)) were conducted on similarly treated cultures, with the dual-emission probe JC-1, and the correlation with the results of the viability experiments were determined.
Results:
The peripheral benzodiazepine receptor agonist PK11195 induced RGC death, but this was not inhibited by cyclosporin A (CsA), which normally maintains the PTP in the closed configuration. Paradoxically, the combination of CsA and PK11195 caused massive RGC death and decreased DeltaPsi(m), suggesting aberrant regulation of the PTP in these cells. Imaging of DeltaPsi(m) revealed morphologic changes in the mitochondria after depolarization, characterized by formation of ringlike bodies, and similar to that with the potassium ionophore valinomycin. There were no such findings with other retinal neurons or neuronally differentiated PC-12 cells. The anomalous RGC death was independent of caspase activation or reactive oxygen species production.
Conclusions:
These results suggest an aberrant opening of the RGC PTP and could be the result of structural differences in its components or its interaction with intracellular ligands. Unique RGC PTP behavior could underlie the pathophysiology of those mitochondrial diseases in which RGCs are specifically affected (e.g., Leber hereditary optic neuropathy).
Insights
The mitochondrial permeability transition pore (PTP) in retinal ganglion cells (RGCs) opens abnormally, leading to cell death. This unique RGC PTP behavior may explain RGC susceptibility in certain mitochondrial diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Mitochondrial Biology
Background:
- Retinal ganglion cells (RGCs) are crucial for vision.
- Apoptosis, or programmed cell death, is a key process in RGC survival and death.
- The mitochondrial permeability transition pore (PTP) is implicated in cellular apoptosis.
Purpose of the Study:
- To investigate the role of the mitochondrial permeability transition pore (PTP) in the apoptosis of axotomized retinal ganglion cells (RGCs) in vitro.
- To understand the specific mechanisms of PTP involvement in RGC death.
Main Methods:
- Primary rat retinal cultures with DiI-labeled RGCs were used.
- Pharmacological agents modulating the PTP were applied.
- Ratiometric imaging of mitochondrial membrane potential (DeltaPsi(m)) using JC-1 was performed.
Main Results:
- PK11195 induced RGC death, unaffected by cyclosporin A (CsA).
- The combination of CsA and PK11195 paradoxically caused massive RGC death and decreased DeltaPsi(m), indicating aberrant PTP regulation.
- Mitochondrial depolarization led to ringlike body formation, distinct from other neuronal cells.
Conclusions:
- Aberrant opening of the RGC PTP suggests unique structural or ligand interaction properties.
- This unique PTP behavior may contribute to RGC vulnerability in mitochondrial diseases like Leber hereditary optic neuropathy.
Related Concept Videos
The Retina
Mitochondrial Membranes
G-Protein Gated Ion Channels
Sensory organs,...
Anatomy of the Eyeball
Photoreceptors and Visual Pathways

