The neural response of a retinal rod to steady illumination fades over time. During a continuous exposure, the phototransduction machinery is reset so that responses to a subsequent intensity change will be enhanced. This process of light adaptation is useful because while we may be creatures of habit, our brains are most interested in change. Exposure to very bright light, either as a flash or as a step, causes a profound loss in sensitivity that far exceeds the loss in quantal catch due to the bleaching of rhodopsin. A 30% bleach suppresses sensitivity in human rods by a millionfold. The Dowling–Rushton relation, formulated 50 years ago, describes the logarithmic decline in sensitivity to light that occurs with the fractional bleach of rhodopsin. Although it was appreciated that bleaching produces a condition in which rods appear to be subjected to a virtual, ‘equivalent’ light, the mechanistic basis was not resolved experimentally until 1994, when Cornwall & Fain (1994) showed that opsin (bleached rhodopsin) weakly activates the phototransduction cascade. This phenomenon is called bleaching adaptation, although from a vision perspective, it is not adaptive at all (reviewed in Lamb & Pugh, 2004). Light isomerizes rhodopsin and causes it to break apart into apo-opsin and all-trans retinal. Retinal is converted to retinol and in the intact eye, the retinol is transferred to neighbouring pigment epithelial cells. In turn these cells provide 11-cis retinal, which binds to opsin to regenerate rhodopsin, enabling rods to emerge from the bleach-adapted state. For physiological studies, it is useful to separate rods from the pigment epithelium in order to prevent regeneration so that bleaching adaptation will last indefinitely. Early work focused on isolated amphibian rods because their large size conferred technical advantages. Although mouse rods are tiny (Fig. 1), the expanding collection of mutant mice with altered phototransduction machinery makes them an inviting resource. One glaring obstacle barred the way. Bleaching more than ∼5% of the rhodopsin in an isolated mouse rod elicits a saturating response from which it never recovers. In a recent issue of The Journal of Physiology, Nymark and colleagues (2012) stepped up to the task. Suspecting that rapid bleaching deluged the rod with toxic retinoids, they tried bleaching the rhodopsin slowly and added albumin to the bath in hopes that it would bind and carry off the retinoids. Figure 1 Isolated salamander (left) and mouse (right) rods at the same magnification Success – the rods survived! Now the partially bleached mouse rods exhibit behaviour characteristic of bleaching adaptation in amphibian rods but with several intriguing differences. Microspectrophotometric measurements revealed that photobleaching was slower for mouse rhodopsin than for human rhodopsin at body temperature and even took longer than amphibian rhodopsin at room temperature. The significance of a slow bleaching process is that it prolongs dark adaptation because until it is complete, photointermediates can repopulate the active state of rhodopsin and produce bursts of cascade activity. Even more surprising, mouse opsin was about a hundred times more effective at activating the phototransduction cascade than amphibian opsin. Since retinoids block the light-regulated ion channels (Dean et al. 2002) and stimulate the activity of opsin, it is no wonder that isolated mouse rods are overwhelmed by relatively small bleaches. Compared with a tiny mouse rod, a given fractional bleach produces a hundred times more opsin in a large salamander rod and there is a fivefold smaller surface-to-volume ratio of the outer segment that must impede the removal of spent retinoid. Opsins are members of the large G protein-coupled receptor family. In general, apo-receptors possess a basal activity. Thus, salamanders were forced to evolve efficient ways of coping with bleaching exposures. Otherwise, a prohibitively long period of dark adaptation would be required before their greater quantal catch could be put to use. One would think that mouse rods would benefit from faster photobleaching and reduced opsin activity. Perhaps evolutionary constraints were relaxed in small mouse rods and measures to suppress apo-opsin activity to the low level in salamander would have come at too high a cost. For example, Nymark et al. (2012) suggest that there may be a tradeoff with energy consumption. Rod diameter can vary by an order of magnitude across fish species. It would be interesting to see whether small fish rods more closely resemble mouse rods while large fish rods more closely resemble amphibian rods with respect to rhodopsin bleaching and bleaching adaptation. Alternatively, ocular circulation, thermoregulation or other factors may be more important than rod size. In the future, it should be possible to trace the bases for species differences in bleaching adaptation to particular modifications in the molecular structures of opsins and to variations in the regulatory control over cascade activity.
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Sep 19, 2013
Hirokazu Katsui + 3
Open Access