Visual function and rhodopsin levels in humans with vitamin A deficiency

The renewal of retinal rod and cone outer segments has been studied by radioautography in rhesus monkeys examined 2 and 4 days after injection of leucine-3H. The cell outer segment consists of a stack of photosensitive, membranous discs. In both rods and cones some of the newly formed (radioactive) protein became distributed throughout the outer segment. Furthermore, in rods (but not in cones), there was a transverse band of concentrated radioactive protein slightly above the outer segment base 2 days after injection. This was due to the formation of new discs, into which labeled protein had been incorporated. At 4 days, these radioactive discs were located farther from the outer segment base. Repeated assembly of new discs had displaced them away from the basal assembly site and along the outer segment. Measurements of the displacement rate indicated that each retinal rod produces 80–90 discs per day, and that the entire complement of outer segment discs is replaced every 9–13 days. To compensate for the continual formation of new discs, groups of old discs are intermittently shed from the apical end of the cell and phagocytized by the pigment epithelium. Each pigment epithelial cell engulfs and destroys about 2000–4000 rod outer segment discs daily. The similarity between visual cells in the rhesus monkey and those in man suggests that the same renewal processes occur in the human retina.

1. Rod dark adaptations after a photoregenerating flash and quantum-equivalent 30 sec bleach are found to be in exact agreement, while the measured rhodopsin regenerations are grossly different. This finding confirms and clarifies "Rushton's paradox', the failure of the Dowling-Rushton equation (linking log sensitivity linearly with unregenerated rhodopsin) to account for human rod dark adaptation after flash photolysis. 2. The hypothesis that the agreement between rod dark adaptation curves after a photoregenerating flash and after a quantum-equivalent 30 sec bleach is coincidental is rejected on the basic of two classes of experiments. 3. Rod "bleaching' adaptation is demonstrated to be entirely determined by the number of rhodopsin molecules which absorb at least one quantum in a temporal period T, whose range includes the time interval 600 musec less than or equal T less than or equal 30 sec. This generalization obtains over the entire scotopic energy range (congruent to 3 log units) where rod dark adaptations has been studied. 4. Thus, the state of "bleaching' adaptation is determined by some by-product of the normal chain of events in scotopic excitation. About this by-product three important deductions are made: (i) its production is a monotonic function of the initial effective quantum absorptions; (ii) its production occurs before the metarhodopsin I leads to to metarhodopsin II dark reaction; (iii) it cannot be any photoproduct of the rhodopsin cycle.