Experimental Degeneration of the Retina I. Thiol Reactors as Inducing Agents

Abstract

USING electroretinography in attempts to elucidate the relative significance of aerobic glycolysis and of respiration in the metabolism of the retina in the intact animal, Noell (1951, a, b) found that intravenous injections of sodium iodoacetate-an inhibitor of glycolysis-extinguished within a few minutes electrical response to illumination of the retina in the cat and rabbit.In confirming these findings, Schubert and Bornschein (1951) drew attention to the extensive destruction of the rod and cone and the outer nuclear layers of the retina induced by the iodoacetate injection-observations also recorded by Noell (1952, a, b). That the relationship between changes in the electrical response and histological damage is not direct is seen from the fact that only functional and no anatomical disturbances are observed after injections of azide (Noell, 1952, a), and of sodium fluorite (Babel and Ziv, 1956). The histological damage induced by iodoacetate has been repeatedly confirmed (Karli, 1952 and1954; de Berardinis and Bonavolonta, 1952; de Berardinis, 1953;and Babel and Ziv, 1956), but the mode of action remains obscure. Remarking on the known ability of iodoacetate to react with thiol groups, Noell (1952, b) observed that many intracellular activities might be affected by this agent. The present investigation was undertaken to determine whether the injurious action-upon the retina is shared by other compounds reactive for thiol groups when given intravenously to the rabbit and rat. Methods and Agents UsedWith sodium iodoacetate in a dose of 29 mg./kg. in the rabbit, ophthalmoscopic and histological lesions essentially similar to those reported by previous observers were obtained. Like Karli, we found it unnecessary to give more than one injection. In the rat, a dose of 42 mg./kg. had to be used, but the effect was less consistent, the lesions being either mild or entirely absent.The various thiol reagents administered are listed in the Table (overleaf). Usually only one injection was given, but some animals received two or three similar injections, generally on consecutive days. The single doses given represented more than 80 per cent. of the minimum lethal dose in nearly every case.In the rabbit, reagents were injected in the ear vein; in the rat, the injection *

Experimental Degeneration of the Retina Ii. The Lesion Produced by Bromoacetate: Ophthalmoscopic and Histological Features

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During the course of an investigation of the effects of various thiol reagents upon the rabbit retina (Sorsby, Newhouse, and Lucas, 1957) it was observed that sodium bromoacetate caused histological damage, the details of which are recorded here.Twelve adult rabbits of mixed stock weighing 1[5 to 2 5 kg. received intravenous injections of from 16 to 32 mg./kg.

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Action of Metabolic Poisons on the Isolated Retina: Relation of Histological to Biochemical Lesions

“…12, overleaf) were similar to those seen in the rabbit, and that the minimal effective concentrations were the same. The sensitivity of the isolated rat retina to either structural damage or metabolic inhibition (Newhouse, 1959) by NaTA contrasts with its relative resistance to damage in the intact animal (Sorsby, Newhouse, and Lucas, 1957).…”

Experimental Degeneration of the Retina Iii. Inhibitors of Glycolysis and of Respiration as Inducing Agents

“…Furthermore, the high glycolytic activity of the retina raises the possibility that retinal degeneration might arise from interference with this activity; indeed, the action of sodium iodoacetate in inducing experimental degeneration has been ascribed to its possible effect on glycolysis. Since iodoacetate is an outstanding thiol reactor, other such reactors were studied and their effects have been recorded previously (Sorsby, Newhouse, and Lucas, 1957;Lucas, Newhouse, and Davey, 1957). With one exception, none of the thiol reactors used produced any experimental lesions in the rat or rabbit, the exception being bromoacetate, an analogue of iodoacetate, and this gave only a mild lesion in the rabbit and none at all in the rat.…”