Biomedical subjects

T D Lamb

Publications and source records attributed to T D Lamb.

At least 19 recordsLinked to original sources

PubMed2006

Dark adaptation of human rod bipolar cells measured from the b-wave of the scotopic electroretinogram.

To examine the dark adaptation of human rod bipolar cells in vivo, we recorded ganzfeld ERGs to (a) a family of flashes of increasing intensity, (b) dim test flashes presented on a range of background intensities, and (c) dim test flashes presented before, and up to 40 min after, exposure to intense illumination eliciting bleaches from a few per cent to near total. The dim flash ERG was characterized by a prominent b-wave response generated principally by rod bipolar cells. In the presence of background illumination the response reached peak earlier and desensitized according to Weber's Law. Following bleaching exposures, the response was initially greatly desensitized, but thereafter recovered slowly with time. For small bleaches, the desensitization was accompanied by acceleration, in much the same way as for real light. Following a near-total bleach, the response was unrecordable for >10 min, but after approximately 23 min half-maximal sensitivity was reached, and full sensitivity was restored between approximately 35 and 40 min. With smaller bleaches, recovery commenced earlier. We converted the post-bleach measurements of desensitization into 'equivalent background intensities' using a Crawford transformation. Across the range of bleaching levels, the results were described by a prominent 'S2' component (0.24 decades min(-1)) together with a smaller and slower 'S3' component (0.06 decades min(-1)), as is found for dark adaptation of the scotopic visual system. We attribute the S2 component to the presence of unregenerated opsin, and we speculate that the S3 component results from ion channel closure by all-trans retinal.

Adaptation, Ocular↗

PubMed2006

The photocurrent response of human cones is fast and monophasic.

BACKGROUND: The precise form of the light response of human cone photoreceptors in vivo has not been established with certainty. To investigate the response shape we compare the predictions of a recent model of transduction in primate cone photoreceptors with measurements extracted from human cones using the paired-flash electroretinogram method. As a check, we also compare the predictions with previous single-cell measurements of ground squirrel cone responses. RESULTS: The predictions of the model provide a good description of the measurements, using values of parameters within the range previously determined for primate retina. The dim-flash response peaks in about 20 ms, and flash responses at all intensities are essentially monophasic. Three time constants in the model are extremely short: the two time constants for inactivation (of visual pigment and of transducin/phosphodiesterase) are around 3 and 10 ms, and the time constant for calcium equilibration lies in the same range. CONCLUSION: The close correspondence between experiment and theory, using parameters previously derived for recordings from macaque retina, supports the notion that the electroretinogram approach and the modelling approach both provide an accurate estimate of the cone photoresponse in the living human eye. For reasons that remain unclear, the responses of isolated photoreceptors from the macaque retina, recorded previously using the suction pipette method, are considerably slower than found here, and display biphasic kinetics.

Animals↗

PubMed2005

Extremely rapid recovery of human cone circulating current at the extinction of bleaching exposures.

We used a conductive fibre electrode placed in the lower conjunctival sac to record the a-wave of the human photopic electroretinogram elicited by bright white flashes, delivered during, or at different times after, exposure of the eye to bright white illumination that bleached a large fraction (approximately 90%) of the cone photopigment. During steady-state exposures of this intensity, the amplitude of the bright-flash response declined to approximately 50% of its dark-adapted level. After the intense background was turned off, the amplitude of the bright-flash response recovered substantially, for flashes presented within 20 ms of background extinction, and fully, for flashes presented 100 ms after extinction. In addition, a prominent 'background-off a-wave' was observed, beginning within 5-10 ms of background extinction. We interpret these results to show, firstly, that human cones are able to preserve around half of their circulating current during steady-state illumination that bleaches 90% of their pigment and, secondly, that following extinction of such illumination, the cone circulating current is restored within a few tens of milliseconds. This behaviour is in stark contrast to that in human rods, where the circulating current is obliterated by a background that bleaches only a few percent of the pigment, and where full recovery following a large bleach takes at least 20 min, some 50,000 times more slowly than shown here for human cones.

Action Potentials↗

PubMed2005

Inverted photocurrent responses from amphibian rod photoreceptors: role of membrane voltage in response recovery.

We recorded photocurrent responses of retinal rods isolated from cane toads Bufo marinus and clawed frogs Xenopus laevis. With the outer segment drawn part way into the suction pipette, presentation of flashes to the base of the outer segment (outside the pipette) elicited a slow inverted response. Stimulation of the same region, with the outer segment drawn fully in, gave a response of conventional polarity. For moderate to bright flashes a fast transient preceded the slow inverted response. Upon bleaching the tip of the outer segment, the slow inverted response was abolished but the fast initial transient remained, and we attribute this fast component to a capacitive current. Experiments employing simultaneous whole-cell patch-clamp and suction pipette recording revealed that both the fast and slow components of the inverted responses were absent in voltage-clamped cells. In current-clamped cells the slow inverted current response was delayed substantially with respect to the voltage response. We present a computational model for the slow component, in which hyperpolarization leads to increased activity of the Na+ -Ca2+, K+ exchanger, hence lowering the cytoplasmic Ca2+ concentration, activating guanylyl cyclase, raising cyclic GMP concentration, opening cyclic nucleotide-gated channels, and increasing circulating current in the unstimulated region. For the measured voltage response to stimulation of the base, we solve these equations to predict the photocurrent in the tip, and obtain an adequate explanation of the inverted responses. Our work suggests a novel role for membrane voltage in accelerating the inactivation phase of the response to light.

Animals↗

PubMed2004

Contribution of cone photoreceptors and post-receptoral mechanisms to the human photopic electroretinogram.

We recorded the electroretinogram (ERG) from human subjects with normal vision, using ganzfeld stimulation in the presence of rod-suppressing blue background light. In families of responses to flashes of increasing intensity, we investigated features of both receptoral and post-receptoral origin. Firstly, we found that the oscillatory potentials (OPs, that have long been known to be post-receptoral) exhibited a time course that was invariant over a range of bright flash intensities. Secondly, we found that the photopic b-wave (which probably originates in cone ON bipolar cells) was most pronounced after test flashes of around 20 Td s, and could be suppressed either by increasing the test flash intensity or by applying a second flash after the test flash. We obtained estimates of the time course of the cone photoreceptor response using the paired-flash technique, in which an intense 'probe' flash was delivered at different times after a test flash. The response to the probe flash was recorded and, its amplitude was measured at early times after the probe flash. Estimates obtained in this way were of normalized amplitude, but could be scaled to an absolute amplitude by making an assumption about the level of probe-flash response that corresponded to complete suppression of photoreceptor current. For moderately bright test flashes the estimated cone photoreceptor response at early times coincided closely with the a-wave of the test flash ERG. However, the maximal size of this estimated response accounted for only about 70% of the peak a-wave amplitude in the case of bright flashes, and for an even smaller proportion after flashes of lower intensity, and we take this to indicate the existence of a third substantial post-receptoral contribution to the a-wave. For dim flashes, the time-to-peak of the cone response was around 15-20 ms, and for saturating flashes the dominant time constant of recovery was about 18 ms. The intensity dependence of the estimated cone response amplitude at fixed times followed an exponential saturation relation. We provide a comparison between our estimates of photoreceptor responses from human cones, and recent estimates from monkey cones obtained using related ERG approaches, and earlier single-cell measurements from isolated primate cones.

Adult↗

PubMed2004

Dark adaptation and the retinoid cycle of vision.

Following exposure of our eye to very intense illumination, we experience a greatly elevated visual threshold, that takes tens of minutes to return completely to normal. The slowness of this phenomenon of "dark adaptation" has been studied for many decades, yet is still not fully understood. Here we review the biochemical and physical processes involved in eliminating the products of light absorption from the photoreceptor outer segment, in recycling the released retinoid to its original isomeric form as 11-cis retinal, and in regenerating the visual pigment rhodopsin. Then we analyse the time-course of three aspects of human dark adaptation: the recovery of psychophysical threshold, the recovery of rod photoreceptor circulating current, and the regeneration of rhodopsin. We begin with normal human subjects, and then analyse the recovery in several retinal disorders, including Oguchi disease, vitamin A deficiency, fundus albipunctatus, Bothnia dystrophy and Stargardt disease. We review a large body of evidence showing that the time-course of human dark adaptation and pigment regeneration is determined by the local concentration of 11-cis retinal, and that after a large bleach the recovery is limited by the rate at which 11-cis retinal is delivered to opsin in the bleached rod outer segments. We present a mathematical model that successfully describes a wide range of results in human and other mammals. The theoretical analysis provides a simple means of estimating the relative concentration of free 11-cis retinal in the retina/RPE, in disorders exhibiting slowed dark adaptation, from analysis of psychophysical measurements of threshold recovery or from analysis of pigment regeneration kinetics.

Animals↗

PubMed2003

Recovery of the human photopic electroretinogram after bleaching exposures: estimation of pigment regeneration kinetics.

We used a fibre electrode in the lower conjunctival sac of the human eye to record the a-wave of the photopic electroretinogram elicited in response to dim red flashes, delivered in the presence of a rod-saturating blue background, before and after exposure of the eye to bright white illumination that bleached a significant fraction of cone photopigment. Responses were recorded from two normal subjects whose pupils were maximally dilated. A range of intensities of bleaching light were used, from 500 to 3000 photopic cd m(-2), and exposures were made sufficiently long in duration to achieve a steady-state bleach. In addition, responses were also recorded following shorter durations of exposures to the highest intensity (3000 cd m(-2)); these durations ranged from 5 to 60 s. The amplitude of the a-wave response to dim flashes was reduced following the exposures, with brighter or longer exposures causing greater reduction. The amplitude then recovered within about 4 min to the prebleach level. The amplitudes measured at ca 15 ms after the flash were used to derive the effective intensity of the flashes, thereby quantifying the fraction of photopigment available at the time of delivery of each flash. Recovery from all exposures in both subjects followed a common time course, which could be described well by a model of pigment kinetics based on rate-limited regeneration, where the initial rate of recovery following a total bleach was ca 50% of the total pigment per minute, and the residual pigment level for half the maximal rate was ca 20% of the total pigment. The same parameters, together with a fixed photosensitivity, could account for the steady-state pigment levels seen at each bleaching intensity, and also for the fraction of pigment bleached following exposures of different duration at the highest intensity. The dim-flash ERG thus provides a novel method for assessing pigment regeneration in vivo. Our finding that pigment regeneration follows rate-limited kinetics may explain previous reports of pigment regeneration deviating from first order kinetics. We present a model of regeneration in which the rate limit arises from a limitation in the delivery of 11-cis-retinoid to the photoreceptor outer segments.

Dark Adaptation↗

PubMed2003

Multiple steps of phosphorylation of activated rhodopsin can account for the reproducibility of vertebrate rod single-photon responses.

Single-photon responses (SPRs) in vertebrate rods are considerably less variable than expected if isomerized rhodopsin (R*) inactivated in a single, memoryless step, and no other variability-reducing mechanisms were available. We present a new stochastic model, the core of which is the successive ratcheting down of R* activity, and a concomitant increase in the probability of quenching of R* by arrestin (Arr), with each phosphorylation of R* (Gibson, S.K., J.H. Parkes, and P.A. Liebman. 2000. Biochemistry. 39:5738-5749.). We evaluated the model by means of Monte-Carlo simulations of dim-flash responses, and compared the response statistics derived from them with those obtained from empirical dim-flash data (Whitlock, G.G., and T.D. Lamb. 1999. Neuron. 23:337-351.). The model accounts for four quantitative measures of SPR reproducibility. It also reproduces qualitative features of rod responses obtained with altered nucleotide levels, and thus contradicts the conclusion that such responses imply that phosphorylation cannot dominate R* inactivation (Rieke, F., and D.A. Baylor. 1998a. Biophys. J. 75:1836-1857; Field, G.D., and F. Rieke. 2002. Neuron. 35:733-747.). Moreover, the model is able to reproduce the salient qualitative features of SPRs obtained from mouse rods that had been genetically modified with specific pathways of R* inactivation or Ca2+ feedback disabled. We present a theoretical analysis showing that the variability of the area under the SPR estimates the variability of integrated R* activity, and can provide a valid gauge of the number of R* inactivation steps. We show that there is a heretofore unappreciated tradeoff between variability of SPR amplitude and SPR duration that depends critically on the kinetics of inactivation of R* relative to the net kinetics of the downstream reactions in the cascade. Because of this dependence, neither the variability of SPR amplitude nor duration provides a reliable estimate of the underlying variability of integrated R* activity, and cannot be used to estimate the minimum number of R* inactivation steps. We conclude that multiple phosphorylation-dependent decrements in R* activity (with Arr-quench) can confer the observed reproducibility of rod SPRs; there is no compelling need to invoke a long series of non-phosphorylation dependent state changes in R* (as in Rieke, F., and D.A. Baylor. 1998a. Biophys. J. 75:1836-1857; Field, G.D., and F. Rieke. 2002. Neuron. 35:733-747.). Our analyses, plus data and modeling of others (Rieke, F., and D.A. Baylor. 1998a. Biophys. J. 75:1836-1857; Field, G.D., and F. Rieke. 2002. Neuron. 35:733-747.), also argue strongly against either feedback (including Ca2+-feedback) or depletion of any molecular species downstream to R* as the dominant cause of SPR reproducibility.

Adenosine Triphosphate↗

PubMed2001

Time course of the flash response of dark- and light-adapted human rod photoreceptors derived from the electroretinogram.

1. The a-wave of the electroretinogram was recorded from human subjects with normal vision, using a corneal electrode and ganzfeld stimulation. We applied the paired-flash technique, in which an intense 'probe' flash was delivered at different times after a 'test' flash. The amplitude of the probe-flash response provided a measure of the circulating current remaining at the appropriate time after the test flash. 2. We extended previous methods by measuring not at a fixed time, but at a range of times after the probe flash, and then calculating the ratio of the 'test-plus-probe' response to the 'probe-alone' response, as a function of time. 3. Under dark-adapted conditions the rod response derived by the paired-flash technique (in response to a relatively dim test flash) peaked at ca 120 ms, with a fractional sensitivity at the peak of ca 0.1 Td(-1) s(-1). 4. As reported previously, background illumination reduced the maximal response, reflecting a reduction in rod circulating current. In addition, it shortened the time to peak (to ca 70 ms at an intensity of 170 Td), and reduced the flash sensitivity measured at the peak. The flash sensitivity declined approximately according to Weber's Law, with a 10-fold reduction occurring at an intensity of 100-200 Td. We could not reliably measure responses at significantly higher background intensities because the circulating current became so small. 5. In order to investigate the phototransduction process after correction for response compression, we expressed the derived response as a fraction of the maximal response that could be elicited in the presence of the background. The earliest rising phase of this 'fractional response per unit intensity' was little affected by background illumination, suggesting that the amplification constant of transduction was unaltered by light adaptation.

Adaptation, Ocular↗

PubMed2000

Human cone photoreceptor responses measured by the electroretinogram [correction of electoretinogram] a-wave during and after exposure to intense illumination.

We recorded the a-wave of the electroretinogram from human subjects with normal vision, using a corneal fibre electrode and ganzfeld stimulation under photopic conditions, so as to extract the parameters of cone phototransduction. The amplitude of bright flash responses provided a measure of the massed circulating current of the cones, while the amplitude of dim flash responses provided a measure of the product of the fraction of cone photopigment present, and the amplification constant of transduction within the cones. In the presence of steady background illumination, the cone circulating current declined to half at 3000 photopic trolands, and to a quarter at 20 000 photopic trolands. At very early times after the delivery of a near-total bleach, we could not determine the level of circulating current as our bright flashes did not appear to saturate the a-wave (presumably because so little pigment was present). However, by 20-30 s after a total bleach, the cone circulating current had returned to its dark-adapted level. Following smaller bleaches (when ca 50 % of the pigment remained present) the bright flashes were able to saturate the a-wave even at very early times. Within 3 s of extinction of the illumination, the cone circulating current had returned to its dark-adapted level. This is at least a factor of 300 times faster than the period of ca 15 min required for full recovery of rods exposed to the same level of bleach, and indicates a major difference between rods and cones in the way that they cope with the photoproducts of bleaching. Despite the very rapid recovery of circulating current after bleaches, the recovery of dim-flash sensitivity was much slower, with a time constant of ca 1.5 min after a near-total bleach. This time course is very similar to previous measurements of the regeneration of cone photopigment, and it seems highly probable that the reduction in dim-flash sensitivity results from pigment depletion.

Adaptation, Ocular↗

PubMed2000

The gain of rod phototransduction: reconciliation of biochemical and electrophysiological measurements.

We have resolved a central and long-standing paradox in understanding the amplification of rod phototransduction by making direct measurements of the gains of the underlying enzymatic amplifiers. We find that under optimized conditions a single photoisomerized rhodopsin activates transducin molecules and phosphodiesterase (PDE) catalytic subunits at rates of 120-150/s, much lower than indirect estimates from light-scattering experiments. Further, we measure the Michaelis constant, Km, of the rod PDE activated by transducin to be 10 microM, at least 10-fold lower than published estimates. Thus, the gain of cGMP hydrolysis (determined by kcat/Km) is at least 10-fold higher than reported in the literature. Accordingly, our results now provide a quantitative account of the overall gain of the rod cascade in terms of directly measured factors.

Animals↗

PubMed2000

The role of steady phosphodiesterase activity in the kinetics and sensitivity of the light-adapted salamander rod photoresponse.

We investigated the kinetics and sensitivity of photocurrent responses of salamander rods, both in darkness and during adaptation to steady backgrounds producing 20-3,000 photoisomerizations per second, using suction pipet recordings. The most intense backgrounds suppressed 80% of the circulating dark current and decreased the flash sensitivity approximately 30-fold. To investigate the underlying transduction mechanism, we expressed the responses as a fraction of the steady level of cGMP-activated current recorded in the background. The fractional responses to flashes of any fixed intensity began rising along a common trajectory, regardless of background intensity. We interpret these invariant initial trajectories to indicate that, at these background intensities, light adaptation does not alter the gain of any of the amplifying steps of phototransduction. For subsaturating flashes of fixed intensity, the fractional responses obtained on backgrounds of different intensity were found to "peel off" from their common initial trajectory in a background-dependent manner: the more intense the background, the earlier the time of peeling off. This behavior is consistent with a background-induced reduction in the effective lifetime of at least one of the three major integrating steps in phototransduction; i.e., an acceleration of one or more of the following: (1) the inactivation of activated rhodopsin (R*); (2) the inactivation of activated phosphodiesterase (E*, representing the complex G(alpha)-PDE of phosphodiesterase with the transducin alpha-subunit); or (3) the hydrolysis of cGMP, with rate constant beta. Our measurements show that, over the range of background intensities we used, beta increased on average to approximately 20 times its dark-adapted value; and our theoretical analysis indicates that this increase in beta is the primary mechanism underlying the measured shortening of time-to-peak of the dim-flash response and the decrease in sensitivity of the fractional response.

Adaptation, Ocular↗

PubMed1999

Light adaptation and dark adaptation of human rod photoreceptors measured from the a-wave of the electroretinogram.

1. We recorded the a-wave of the human electroretinogram from subjects with normal vision, using a corneal electrode and ganzfeld (full-field) light stimulation. From analysis of the rising phase of rod-isolated flash responses we determined the maximum size (amax) of the a-wave, a measure of the massed circulating current of the rods, and the amplification constant (A) of transduction within the rod photoreceptors. 2. During light adaptation by steady backgrounds the maximal response was reduced, as reported previously. amax declined approximately as I0/(I0 + IB), where IB is retinal illuminance and I0 is a constant. In different subjects I0 ranged from 40 to 100 trolands, with a mean of 70 trolands, corresponding to about 600 photoisomerizations s-1 per rod. (1 troland is the retinal illuminance that results when a surface luminance of 1 cd m-2 is viewed through a pupil area of 1 mm2.) The amplification constant A decreased only slightly in the presence of steady backgrounds. 3. Following a full bleach amax recovered along an S-shaped curve over a period of 30 min. There was no detectable response for the first 5 min, and half-maximal recovery took 13-17 min. 4. The apparent amplification constant decreased at early times after large bleaches. However, upon correction for reduced light absorption due to loss of pigment, with regeneration of rhodopsin occurring with a time constant of 9-15 min in different subjects, it appeared that the true value of A was probably unchanged by bleaching. 5. The recovery of amax following a bleach could be converted into recovery of equivalent background intensity, using a 'Crawford transformation' derived from the light adaptation results. Following bleaches ranging from 10 to > 99 %, the equivalent background intensity decayed approximately exponentially, with a time constant of about 3 min. 6. The time taken for amax to recover to a fixed proportion of its original level increased approximately linearly (rather than logarithmically) with fractional bleach, with a slope of about 12 min per 100 % bleach. Similar behaviour has previously been seen in psychophysical dark adaptation experiments, for the dependence of the 'second component' of recovery on the level of bleaching.

Adaptation, Ocular↗

PubMed1999

Variability in the time course of single photon responses from toad rods: termination of rhodopsin's activity.

We examined the responses of toad rod photoreceptors to single photons of light. To minimize the effects of variability in the early rising phase, we selected sets of responses that closely matched the rise of the mean single photon response. Responses selected in this way showed substantial variations in kinetics, appearing to peel off from a common time course after different delays. Following incorporation of the calcium buffer BAPTA, the time to peeling off was retarded. Our analysis indicates that it is not necessary to invoke a long series of reaction steps to explain the shutoff of rhodopsin activity. Instead, our results suggest that the observed behavior is explicable by the presently known shutoff reactions of activated rhodopsin, modulated by feedback.

Algorithms↗

PubMed1999

Molecular mechanisms of vertebrate photoreceptor light adaptation.

An important recent advance in the understanding of vertebrate photoreceptor light adaptation has come from the discovery that as many as eight distinct molecular mechanisms may be involved, and the realization that one of the principal mechanisms is not dependent on calcium. Quantitative analysis of these mechanisms is providing new insights into the nature of rod photoreceptor light adaptation.

Adaptation, Ocular↗

PubMed1998

Molecular basis of dark adaptation in rod photoreceptors.

Following exposure of the eye to an intense light that 'bleaches' a significant fraction of the rhodopsin, one's visual threshold is initially greatly elevated, and takes tens of minutes to recover to normal. The elevation of visual threshold arises from events occurring within the rod photoreceptors, and the underlying molecular basis of these events and of the rod's recovery is now becoming clearer. Results obtained by exposing isolated toad rods to hydroxylamine solution indicate that, following small bleaches, the primary intermediate causing elevation of visual threshold is metarhodopsin II, in its phosphorylated and arrestin-bound form. This product activates transduction with an efficacy about 100 times greater than that of opsin.

Animals↗

PubMed1997

Effect of hydroxylamine on photon-like events during dark adaptation in toad rod photoreceptors.

1. The suction pipette technique was used to investigate the recovery of toad rod photoreceptors following small bleaches of 0.2-3% of the rhodopsin. 2. The reduction in sensitivity and the increase in noise elicited by bleaches were measured, and from these measurements the underlying rate of occurrence of photon-like events was calculated as a function of time after the bleach. 3. Exposure to hydroxylamine solution was used to hasten the decomposition of the metarhodopsin photoproducts. The outer segment was exposed to 110 mM hydroxylamine in a low-Ca2+ Ringer solution for a period of 10-50 s beginning 10-17 min after the bleaching exposure. 4. By the time of the hydroxylamine exposure, the flash sensitivity and response kinetics had returned almost to normal, and were not significantly altered by the exposure. 5. Following hydroxylamine exposure, the rate of spontaneous photon-like events in the rods declined rapidly to near pre-bleach levels. 6. We conclude that hydroxylamine reduces the rate of occurrence of photon-like events induced by a bleach, and we postulate that this reduction results from the removal of metarhodopsin (most likely metarhodopsin II) from the outer segment. 7. Our results are consistent with a model in which photon-like events result from reversal of the reactions (phosphorylation and capping by arrestin) that lead to inactivation of the activated form of rhodopsin, Rh*.

Adaptation, Physiological↗

PubMed1997

The a-wave of the human electroretinogram recorded with a minimally invasive technique.

A minimally invasive technique is described for recording the a-wave of the human ERG and extracting the parameters of transduction in the rod and cone photoreceptors. A corneal DTL fibre electrode is used, but the pupil is not dilated and the cornea is not anaesthetized. Although the amplitude of the signal collected by the DTL electrode varies from session to session, this is not a problem, as the photoreceptor fractional circulating current is obtained by normalization of the response family. A method is described for varying the effective flash intensity over a wide range, by controlling the duration of the xenon flash. In order to fit the kinetics of the responses, an analytical equation is derived for the convolution of the previous "delayed gaussian" expression with the cell's capacitive time constant. This equation provides a good description of both the rod and the cone response families. For rods, the capacitive time constant was found to be tau rod approximately 1 msec as reported previously, but for the cones a considerably longer time constant of tau cone approximately 4-5 msec was needed. For rods, the amplification constant (Arod approximately 5 sec-2) was close to previous estimates, but for cones the sensitivity (expressed in terms of corneal illuminance) was higher than in previous work. Calculation of the amplification constant of transduction within the cones requires knowledge of their light collection properties, and the absence of hard information makes this estimate somewhat speculative. However, when account is taken of the larger diameter of the inner segments of cones in the peripheral retina, then our estimated amplification constant for the cones (Acone approximately 3-7 sec-2) is of a similar order of magnitude to that obtained for the rods.

Adult↗