EFFECTS ON THE RETINA AND THE EYE 237 



the retina: the retinal neuroglia reacts and numerous mitoses are seen in 

 the internal granular layer, the pigmentary epithelium presents areas of 

 localized proliferation, and some degeneration is evident in the external 

 granular layer. Karli concluded that a pigmentary retinosis is produced 

 secondary to the primary effect on the visual cells. There is a great sim- 

 ilarity between the picture produced by iodoacetate and the hereditary 

 human degenerative disease of retinitis pigmentosa, and it is interesting 

 to speculate that some metabolic lesion due to a genie aberration is present 

 in this disease. Pigmentary clumping has been observed histologically (Noell, 

 1952) and ophthalmoscopically (Lucas et al, 1957), and pigment cell mi- 

 gration (Rabinovitch et al, 1954) and proliferation (Karli, 1954; Babel and 

 Ziv, 1956) also occur. 



Noell (1952) described many of the later degenerative changes in greater 

 detail in rabbits, cats, and monkeys, and the following additional observa- 

 tions may be noted. (1) No ERG is detectable after 3 weeks and yet stimu- 

 lation of the optic nerve gives a normal striate reaction, showing the effect 

 to be all distal. (2) No histological changes can be detected in the optic 

 nerve. (3) The destruction of the visual cells, with nuclear pycnosis and 

 death of the rod cells, occurs less than 24 hr after the injections, showing 

 a fairly rapid killing action on these cells. (4) The cone cells exhibit remark- 

 able changes: a swelling of the ellipsoidal body followed by longitudinal 

 shrinkage, with destruction of all special organelles, so that the cells even- 

 tually appear as a row of simple epithelium, as if dedifferentiation had oc- 

 curred. (5) The cone cells are damaged more and more as their distance 

 from the fovea increases. Some of these effects might be interpreted as due 

 to disturbances in the blood flow, but reduction of the flow to the retina 

 does not induce similar changes. The chick retina, which is quite sensitive 

 to iodoacetate, shows less differential effect, the whole retinal structure be- 

 ing grossly disturbed (Rabinovitch et al, 1954). Selected illustrations of 

 retinal alterations are given in Fig. 1-25. 



Electron microscopy studies by Lasansky and De Robertis (1959) dem- 

 onstrate that lesions of the outer segments of the rod cells occur as early 

 as 3 hr after a single injection of iodoacetate (20 mg/kg), and after 6 hr 

 there are disorganization, vesiculation, and lysis of the rod sacs. The typical 

 multilamellar structure of the rods is disorganized very early and the en- 

 doplasmic reticulum shows vacuolization. A second injection leads to com- 

 plete destruction of the rods, but also destroys cone cells, which are more re- 

 sistant and do not suffer markedly from a single injection. The authors sug- 

 gest that iodoacetate affects some system responsible for the maintenance 

 of membranes or lamellae within the cells. Cibis et al. (1957) found the 

 histological lesions produced by iodoacetate to be very similar to those 

 resulting from X-radiation, a comparison also made by Kent (1959), but it 

 is doubtful if it is profitable to extend further these superficial similarities. 



