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­epithelium, a tissue lining the fundus of the eye and in intimate contact with the rods and cones, played a crucial role in the ­regeneration process, since the synthesis of rhodopsin from vitamin A did not occur in a retina detached from the pigment epithelium. The significance of this dependence was, however, unknown (see Wald, 1935/1936,

p. 367). (Even today the transport pathway from the outer segment of the receptors to the pigment epithelium and back again, and the specific mechanisms by which the transformation­ from vitamin A to 11-cis retinal occurs are not fully known.) Nevertheless, Wald presumed that opsin trapped 11-cis retinal as fast as it appeared to form the visual pigment and hence regulated how much vitamin A was oxidized and visual pigments synthesized. In fact, Wald held that with different opsins went differences in both the kinetics of bleaching and regeneration, and in the absorption spectrum (see Wald, 1968).

18.2  Serious challenges to the photochemical theory

Despite the great contributions of Hecht and Wald, the photochemical theory of adaptation presented did not gain general acceptance. The main obstacle was the well-known fact that sensitivity measured psychophysically by threshold intensity was dependent upon the size of the test field. This finding had generally been explained by assuming that impulses from widely separated retinal areas converged on common pathways and thereby increased the sensitivity. Thus, in addition to the concentration of photoproducts, this convergence factor based on neural summation might influence sensitivity during dark and light adaptation (see e.g. Lythgoe, 1940).

18.3  The neural factor refuted

The view that neural summation influenced the sensitivity increase during dark adaptation was challenged by Hecht, Haig and Wald (1935/1936). The evidence they presented indicated that changes in sensitivity with test area were due principally, not to the change in the area itself, but to variation in the rod-cone composition of the

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test field. Hence, to explore the influence of area specifically as area of sensitivity during dark adaptation, it would be necessary to confine the measurements to retinal areas essentially homogeneous in sensitivity.

Wald (1937/1938), therefore, in a follow-up study, measured the dark adaptation curves with test fields of angular diameters of 1º, 2º, 3º, 4º and 5º at 15º and 25º above the fovea. The results, however, clearly showed that even in these relatively homogeneous regions, the sensitivity increased markedly with test area: at 15º a seven-fold lowering of threshold, at 25º a ten-fold lowering.

Yet, Wald (1937/1938) held that this increase in sensitivity with area did not contradict the photochemical theory, since it could reasonably be accounted for by the simple properties of a mosaic retina with a population of relatively independent units. His analysis of the measurements was based on the assumptions that (1) a threshold response involved the activity of a fixed number of retinal elements, and (2) throughout all portions of the homogeneous retinal field the percentage of such elements was the same. Thus, he presumed that in a series of fields of various sizes the threshold intensity obtained would always correspond to the activation of a constant number of elements, and that the number of elements would be directly proportional to the field area.

Based on these assumptions Wald (1937/1938) arrived at a relatively simple formula, which could accurately describe the change in threshold intensity with area:

(A − nt)k × I = C

where A = area of test field, nt = the constant number of elements for a threshold response, I = threshold test intensity, and k and C = constants.

An important feature of this model was the assumption that the mosaic character of the retina was transferred relatively intact as far as to the occipital cortex. Nevertheless, he did not preclude the possibility of some integration of the responses from the individual

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elements that could increase sensitivity somewhat. Such interaction, however, was assumed to take place somewhere in the brain.

The equation found for the extrafoveal test fields was also assumed to be valid for the central foveal area, where the constant

number of elements for a threshold response (nt) was presumed to be represented by cone receptors. Since in this case (nt) was assumed to be very small, the threshold-area equation was reduced to the simple form:

Ak × I = C

This presumption was supported by available data obtained within the central fovea.

The mosaic theory offered by Wald may be seen as a successful attempt to rescue the photochemical theory. Yet, there still remained a serious challenge to this theory. Thus, it had been found that the ordinary dark-adaptation curve proceeded faster and further as size of the test field increased, while the change in concentration of a photopigment during dark adaptation, on the other hand, would follow the same course irrespective of test size. Apparently, a neural factor had to be involved to explain the dark-adaptation process.

Wald (1958), however, argued that the change in sensitivity obtained was just what one would expect provided it was determined by the synthesizing of a photochemical pigment in a large number of receptors. Thus, one would expect the dark-adaptation curve to reflect, from moment to moment, the activation of a sample of the most sensitive receptors from a population of hundreds or thousands of receptors. Different receptors would then be involved in threshold determination at different times during the dark-adaptation period. Hence, the larger the population, i.e. the larger the test field, the further the dark-adaptation curve would be expected to depart from the adaptation curve of a single rod or cone, yielding a more rapid and extensive adaptation the larger the field.