The retinoid cycle and visual threshold during dark adaptation

Several theories have explored the close relationship between the retinoid cycle and visual threshold during dark adaptation, namely; the photochemical and equivalent background hypotheses.

1.3.4.1. The photochemical hypothesis

It was originally proposed that the visual threshold during dark adaptation was directly proportional to the amount of unbleached photopigment (Hecht et al., 1937), i.e. a 50%

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bleach of photopigment would cause threshold to double. However, this hypothesis was later disproved when retinal densitometry data showed that although both the regeneration of rhodopsin and visual threshold during dark adaptation followed an exponential time course, threshold remained elevated by 3 log units after 90% of rhodopsin had regenerated (Campbell & Rushton, 1955).

Following work in the albino rat (Dowling, 1960) and a rod monochromat (Rushton, 1961), it was proposed that the logarithm of the visual threshold during dark adaptation was proportional to the concentration of bleached rhodopsin. This relationship between threshold and bleached rhodopsin is known as the Dowling-Rushton relationship (Equation 1a) and for many years it was adopted as a comprehensive explanation of dark adaptation. The relationship was later also shown to provide an appropriate description of the regeneration of cone photopigment (Hollins & Alpern, 1973).

Equation 1a. log(It/Ia) = αB

where It is the visual threshold at a given time, Ia is the final dark adapted threshold, α is a constant and B is the proportion of bleached rhodopsin.

The Dowling-Rushton relationship was subsequently shown to be restricted to the description of dark adaptation under specific conditions only (Lamb, 1990; Lamb & Pugh, 2004). When a low intensity photopigment bleach is administered, the initial threshold recorded is markedly higher than that predicted by the model, whereas at large bleaching intensities, the initial threshold is lower than predicted (Lamb, 1990). In addition, the constant ‘α’ included in the model has been shown to vary with the bleaching intensity and is therefore not actually a constant (Pugh, 1975).

1.3.4.2. The equivalent background hypothesis

Stiles and Crawford (1932) proposed that the elevation of threshold at any given time during dark adaptation may be described by an ‘equivalent background’. This theory suggests that sensitivity during dark adaptation is equivalent to that produced by exposure to an adapting light (the so-called ‘equivalent background’) and that this equivalent background has the same effect on vision as a real background light (Stiles & Crawford,

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1932). Consequently, dark adaptation is considered to be a unique form of light adaptation, in which the adaptational state is quantified in terms of the intensity of a steady background light that would produce an equal desensitization of the retina. During dark adaptation, the equivalent background gradually fades and correspondingly, threshold decreases. The decay of the equivalent background was proposed to be related to a hypothetical photoproduct of bleaching (Stiles & Crawford, 1932).

Figure 1.15. Dark adaptation functions (left panel) and increment threshold functions

(right panel), recorded in response to a range of stimuli. Threshold at any given time in the dark may be described in terms of the adapting background that produces the same increment threshold as that recorded in the dark (Blakemore and Rushton, 1965).

The equivalent background hypothesis states that threshold elevation, spatial resolution and temporal resolution measured at any given time during dark adaptation should be equivalent to those measured in the presence of a real background light. This was demonstrated by Blakemore and Rushton (1965). Dark adaptation and increment threshold functions were recorded using a range of stimuli, in a rod monochromat, (Figure 1.15). Although the shape of the dark adaptation curve and increment threshold function were different, for all stimuli the threshold at any given time in the dark was equivalent to that measured on a steady background. However, there is evidence to suggest that the equivalent background hypothesis breaks down under certain conditions, for example when the temporal modulation threshold is measured after exposure to a long, dim adapting light (Hayhoe & Chen, 1986).

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Researchers have proposed that the photoproduct responsible for generating the equivalent background (and therefore threshold elevation) during dark adaptation is likely to be a metarhodopsin photoproduct, such as free-opsin or all-trans retinal (Lamb & Pugh, 2004). In the 1960s, threshold elevation was shown to be associated with the presence of metarhodopsin photoproducts (Donner & Reuter, 1967). Some years later, when rod dark adaptation data were collected at a range of bleaching intensities, the recovery of the logarithm of visual threshold was accurately described by three straight lines with recovery constants of 5, 100 and 400 seconds (Lamb, 1981). It was proposed that these distinct components were generated by the presence of metarhodopsin photoproducts (Lamb, 1981). Additional evidence for the relationship between metarhodopsin photoproducts and visual threshold elevation emerged from work with the inorganic compound hydroxylamine (Leibrock et al., 1998). When added to rod photoreceptors hydroxylamine was shown to expedite threshold recovery during dark adaptation (Leibrock et al., 1998). As hydroxylamine is known to destroy metarhodopsin, this strongly implied that metarhodopsin photoproducts contribute to the elevation of visual threshold.

As discussed (Section 1.3.2, Page 34), regeneration of visual pigment during dark adaptation requires the recombination of 11-cis retinal with free-opsin. The free-opsin formed when metarhodopsin is hydrolysed has been proposed to be responsible for threshold elevation during dark adaptation, particularly during the second component of rod recovery (Lamb & Pugh, 2004). The time course of threshold recovery during the second component of rod dark adaptation is therefore determined by the removal of opsin as it recombines with 11-cis retinal.