EFFECTS ON THE RETINA AND THE EYE 239 



potentiation is unknown; the effect of malate may not be on the retina but 

 perhaps through some systemic changes, such as in the blood pH, altering 

 the rate of penetration of iodoacetate into the retina. Some protective effect 

 is observed in the retina by cysteine given intravenously 90 min before and 

 after iodoacetate at a dose of 300 mg/kg (Sorsby and Harding, 1960), but 

 inspection of the data shows the protection to be quite weak, as would be 

 expected with this schedule. 



Lens 



Cataract has generally been explained as due to an opacity resulting from 

 a defect in the carbohydrate metabolism of the lens. For this reason Nord- 

 mann et al. (1954) applied various inhibitors to perfused calf lenses for fairly 

 long periods of time and then examined the tissue for metabolic and opacity 

 changes. Iodoacetate causes clouding of the lens more rapidly than the other 

 inhibitors (within 2 hr), but was used at the unfortunately high concentra- 

 tion of 21.6 mM. Even at this concentration the lens lactate and ATP 

 levels are not markedly reduced. Cibis and Noell (1955) chose the more 

 obvious approach and injected iodoacetate intravenously into rabbits (20 

 mg/kg) in two doses 6-8 hr apart. The animals were examined 2 months 

 later. The development of opacification accompanied by numerous vacuoles, 

 granules, and a subcapsular iridescence was observed and, histologically, a 

 swelling of the lens fibers, vacuolization of the posterior cortex, and defor- 

 mation and displacement of the epithelial cells. Lenticular changes were 

 noted in about 65% of the rabbits and were said to resemble the effects of 

 X-radiation (Cibis et al, 1957). Iodoacetate at 5 mM inhibits the penetra- 

 tion of glucose into the lens but probably less than 35% (Miiller, 1939). The 

 ion and water pumps in lens are apparently inhibited by iodoacetate, since 

 K+ is lost and Na+ a d water gained, although 6 hr in 25 mM iodoacetate 

 could scarcely be used to interpret the effects in vivo (Harris and Gehrsitz, 

 1951). However, Kinoshita et al. (1961) found the transport systems to be 

 quite sensitive to iodoacetate, since even 0.03 mM exerts a marked inhi- 

 bition of K+ uptake and Na+ extrusion over 20 hr. The uptake of phosphate 

 by rabbit lens is 57% inhibited by 4.8 mM iodoacetate, and there is a sub- 

 stantial loss of ATP (Miiller and Kleifeld, 1953). Whether these actions 

 relate in any way to the development of lens opacity is not known. 



Other Eye Tissues 



Intravenous injections of 20 mg/kg iodoacetate were noted by Cibis et al. 

 (1957) to inhibit aqueous fluid secretion by the ciliary processes, since there 

 is a fall in the intraocular pressure by 2 days, reaching a minimum in 3 days, 

 and recovering in 5-7 days. The actual rate of aqueous flow is depressed 

 27% at 2 days and 58% at 3 days by two spaced injections of iodoace- 

 tate. The glycolytic rate in the ciliary processes is quite high and was esti- 



