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

Abstract

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. sodium bromoacetate. In three animals the dose was repeated on the following day. The nine survivors were killed for histological examination 3 to 21 days after injection.Two animals received combined injections of sodium bromoacetate (16 mg./kg.) and sodium iodoacetate (16 mg./kg.) and were killed 7 days later. All doses are quoted in terms of sodium salt.The solutions for injection were prepared immediately before use by neutralizing the free acid and making up to volume with phosphate buffer. The eyes were fixed in acid Zenker's solution immediately after death. After removal of the lens, paraffin sections were cut and stained by ordinary haematoxylin and eosin, and by Mallory's phosphotungstic acid haematoxylin. Observations Ophthalmoscopic FindingsRetinal haze, probably due to oedema, was usually observed on the day after injection of doses of 32 mg./kg.; 2 days lter, this effect had diminished and faint pigment clumping was apparent. By 10 days after injection, the pigmentary disturbance in the mid-ventral region had assumed a cobblestonelike appearance; the central fundus showed many yellow spots, but the area above the disc appeared almost normal. No further changes were observed a week later. After the mixtures of iodoacetate and bromoacetate the appearances were similar.Histological Findings (i) After single doses of 16-23 mg./kg. of bromoacetate, three rabbits showed no retinal damage.(ii) After two injections of 23 mg./kg. of bromoacetate, one rabbit showed a very localized loss of visual cells in the area centralis when examined a *

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

“…The histological changes caused by sodium bromoacetate, particularly in the visual cell layer, were less marked than those of NaIA. This lesser severity corresponds to that already observed upon the retina in vivo (Lucas, Newhouse, and Davey, 1957). lodoacetamide was less effective as a glycolytic inhibitor than its parent acid, but produced cytological changes of comparable severity (Fig.…”

“…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).…”

“…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.…”

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

“…These changes, obtained with a dose of 32 mg./kg., were similar to those obtained with iodoacetate in doses of 29 mg./kg., differing mainly in being rather milder and largely restricted to the central area. They are described in detail elsewhere in this issue (Lucas, Newhouse, and Davey, 1957). …”

Ophthalmic Pharmacology and Toxicology

“…88,74 Iris and Pupil.-Little new concerning toxic involvement of either pupillary mo¬ tion or accommodation has appeared in the past year, but additional cases have been reported of mydriasis and cycloplegia from exposure to dusts and seeds of Jimson weed 138 and of miosis and blurred vision from cyclotonia induced by parathion.60 These latter effects have attracted attention recently particu¬ larly because of a close resemblance to the effects induced by high-intensity ionizing radiation.…”