Action of metabolic poisons on the isolated retina; relation of histological to biochemical lesions.

NOELL (1952, 1953a, b, 1955) reported that sodium iodoacetate (NaIA), administered intravenously to rabbits, selectively destroyed the visual cells of the retina, an effect he attributed to interference with glycolysis. In previous work (Sorsby, Newhouse, and Lucas, 1957), we investigated the effects on the retina of a wide range of thiol reagents, administered intravenously at maximum tolerated dosage to rats and rabbits. Of these, only iodoacetate (and bromoacetate in the rabbit) caused visible damage to the retina. In the intact animal, blood-retinal barriers and systemic detoxicating and excreting mechanisms are complicating factors which cannot be assessed. Furthermore, the maximum feasible dose is determined not by the sensitivity of the retina but by systemic lethality of the compound given. These difficulties could be avoided by studying the short-term effects of iodoacetate and other inhibitors on the isolated retina, maintained in vitro in a saline medium. By this means, one of us (Newhouse, 1959) has already found that several thiol reagents are able to inhibit retinal glycolysis almost as readily as NaIA, while others are able to depress respiration even more effectively. It seems doubtful therefore whether the singular retinal necrosis that follows parenteral iodoacetate is due simply to glycolytic inhibition. The present studies were made to determine whether, in the isolated retina, any relationship could be demonstrated between the known ability of NaIA and other thiol reagents to inhibit respiration, glycolysis, or both, and their capacity to cause cellular damage.