EFFECTS ON THE RETINA AND THE EYE 235 



of much significance in the effects of iodoacetate on the retina. The uptake 

 and accumulation of K+ in retina depends, as in brain, on the presence of 

 both ghicose and ghitamate. Iodoacetate at 1 niM abolishes the uptake of 

 glutamate and the formation of glutamine in retina, and simultaneously 

 not only prevents accumulation of K+ but induces a marked loss from the 

 cells (Terner et al., 1950). Such an action may help to explain the reduction 

 of the retinal potentials by iodoacetate. 



The close relationship between glycolysis and retinal function is suggested 

 by the excellent work of Noell (1951) at Randolph Field. A rabbit injected 

 intravenously with 15 mg/kg iodoacetate shows a decline in the electrore- 

 tinogram (ERG) b wave within 20 sec and a decline of the response in the 

 optic nerve; the 6 wave vanishes in 2 min. The a wave is not affected at 

 this time, but soon declines and after 20 min has disappeared, so that now 

 no response to illumination can be obtained. The minimal effective dose is 

 2 mg/kg. The dosage used above might be expected to produce a plasma 

 concentration of around 0.5 mM, which could certainly inhibit retinal gly- 

 colysis.* Indeed, it has been shown histochemically that retinal 3-PGDH 

 is inhibited quite significantly at the time of extinction of the ERG (For- 

 gacs, 1963). Retinal potentials in the cat are impaired even more rapidly, 

 both ERG waves declining simultaneously and failing within 2 min, but in 

 the frog the rate of action and the sensitivity are less than in rabbits. The 

 effect of iodoacetate on the ERG potentials is different from that of anoxia 

 or general metabolic depression. Recordings from microelectrodes placed in 

 the retinal cells show that the effect of iodoacetate is to impair the excitatory 

 processes activated by illumination. At these dosage levels and times, there 

 are only minor effects on the cardiovascular and central nervous systems. 

 No other vertebrate tissue function seems so dependent on glycolysis, and 

 perhaps the first effect of iodoacetate is to blind the animal. This initial 

 work has been extended in various directions and we shall confine ourselves 

 for the present to the acute effects, leaving the damage and degeneration of 

 the retina for later discussion. 



The observations of Noell have been confirmed in several reports and 

 with different species; although species may differ in sensitivity, they all 

 respond in the same basic manner. Along with the b wave depression in 



* Since this concentration would be expected to inhibit glycolysis in other tissues 

 as well, the problem comes up of the penetration of iodoacetate into the various tissues 

 Other neural tissues, especially in the central nervous system, are probably relatively 

 impermeable to iodoacetate. The remarkable rapidity with which iodoacetate affects 

 the retina indicates that the retina must be not only very susceptible but also very 

 accessible. The iodoacetate need not enter the cells to produce these membrane elec- 

 trical changes, but one must assume even here that the rate of reaction with SH 

 groups is much faster than is usually observed. These problems of differential pene- 

 trability and selective effects on the retina have in general been ignored. 



