690 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



too - 



80- 



V 60 

 o 



0) 

 



R, 



Vitamin A 



deficient rats 



live 



5 6 7 8 

 WeeKs on diet 



FIG. 24. Vitamin A deficiency in the rat. Blood vitamin .\ 

 (CD) falls precipitously as liver stores of vitamin .-^ (S) are 

 exhausted. At this point, the rhodopsin content of the dark- 

 adapted eye (O) begins to decline, presumably because not 

 enough vitamin .\ is available to convert all the opsin of the 

 rods to rhodopsin. About three weeks later, opsin itself (•) 

 begins to disappear, its concentration from then on paralleling 

 the decreasing rhodopsin content. Disappearance of opsin 

 may in part be responsible for the degeneration of rods and 

 cones associated with chronic vitamin .-\ deficiency. [From 

 Dowling & VVald (12a).] 



retina among others (36, 54). Johnson has reported 

 that after 7 to 13 weeks of vitamin A deprivation in 

 young rats, the rods in the retinal fundus exhibit 

 marked changes. Many outer segments have dis- 

 appeared and those that remain stain aljnormally. 

 As the deficiency progresses, the inner segments of 

 the rods also degenerate, then successively the ex- 

 ternal limiting membrane and outer nuclear layer, 

 the pigment epithelium, the outer molecular layer, 

 and the inner nuclear layer. These changes progress 

 much faster in the central retina than toward the 

 periphery. Outer segments of rods which have suffered 

 only slight degenerative changes seem to repair 

 considerably within 24 hours of vitainin A therapy. 

 Even rods which have degenerated completely 

 appear to regenerate within 10 to 18 weeks of \itamin 

 A administration. 



The rod outer seginent is composed in considerable 

 measure of rhodopsin (see above). A loss of opsin 

 might therefore profoundly damage its structural 

 integrity; long before such changes are visible in 

 the micro.scope they might become detectable physi- 

 ologically as night blindness. In any case, night 

 blindness clearly involves far more than the simple 

 decline of \itamin A concentration in the retina. 

 It introduces, particularly in prolonged deficiency, 

 deep-seated anatomical changes and these might 

 repair only very slowly. 



In addition to deficiency in the diet, any inter- 

 ference with the flow of vitamin A to the retina, or 

 with its uiilization by the tissues can be expected to 

 react on the visual threshold. This appears to be the 

 case in certain chronic liver diseases (cf. 41). Bile 

 is needed for the absorption of both carotene and 

 \itamin A (25). In obstructi\e jaundice, in which 

 bile fails to reach the intestine, vitamin A deficiency 

 and hence night Ijlindness may develop in spite of a 

 diet adecjuate to meet normal requirements. In ad- 

 dition to producing the bile, the li\er is the principal 

 storage tissue for vitamin .\. It is not surprising 

 therefore that liver disorders may affect the extent, 

 and apparently in some instances also the rate, of 

 dark adaptation. 



Recently it has been shown that the wall of the 

 intestine is probably the principal site for the con- 

 version of carotene to \itamin A (14, 55). It is not 

 unlikelv that conditions exist in which some failure 

 of this process leads to \isual disturbances. 



Even when the diet is adequate, and the liver and 

 intestine are performing their functions, this may 

 not yet be enough. \'ision depends, not merely on 

 \itamin A, but on a particular shape of vitamin A, 

 the nco-h isomer. This is not ordinarily present in 

 the food, so that other isomers of vitamin A obtained 

 in the diet must be converted into this special con- 

 figuration. The neo-fe isomer is continuously lost 

 in the bleaching of the visual pigments and must be 

 continuously replaced for vision to persist. It is not 

 impossible that there exists a visual disorder that 

 has its source in a failure to isomerize vitamin A. 

 Furthermore, the fact that \itamin A is stored in the 

 eye as an ester, which must presumably be hy- 

 drolyzed before entering the \isual cycle, constitutes 

 another point at which \isual processes are vulnerable 

 to metabolic failure. 



It has repeatedly been suggested that retinitis 

 pigmentosa, a degenerative disease which attacks 

 primarily the layer of rods and cones, is due to some 



