A model for the formation of ring mitochondria in retinal pigment epithelium.

Purpose: To investigate the mechanism and sequence of formation of ring-shaped mitochondria in retinal pigment epithelial cells of a chick model of gyrate atrophy.

Methods: Electron microscopic analysis of the ultrastructure of retinal pigment epithelial (RPE) mitochondria was carried out in chicks injected intravitreally with formoguanamine regularly (every 4 days) over the first 2 weeks or 4 weeks post-hatching. Formoguanamine is a triazine drug which induces hyperornithinemic symptoms in the chick eye similar to those seen in human gyrate atrophy.

Results: A large population of irregularly shaped mitochondria was observed in the RPE of both peripheral and central retina. They showed extensive morphological changes. At 2 wk, the mitochondria appeared enlarged and abnormal in shape with vacuolisation, partial loss of their double membrane and reduced mitochondrial cristae. By 4 wk, the mitochondria had assumed a rounder, almost circular profile, many with central holes, so-called ring mitochondria.

Conclusion: The appearance of ring-shaped mitochondria has been previously ascribed to the section of cupshaped three-dimensional structures. We present evidence that ring-shaped mitochondrial profiles arise through at least two different mechanisms of membrane breakdown and intraorganelle vacuolisation. The nature of the three dimensional structures of these abnormal mitochondria is re-examined.