The photovoltage of macaque cone photoreceptors: adaptation, noise, and kinetics

Whole-cell voltage and current recordings were obtained from red and green cone photoreceptors in isolated retina from macaque monkey. It was demonstrated previously that the cone photovoltage is generated from two sources, phototransduction current in the cone outer segment and photocurrent from neighboring rods. Rod signals are likely transmitted to cones across the gap junctions between rods and cones. In this study, the "pure" cone and rod components of the response were extracted with rod-adapting backgrounds or by subtracting the responses to flashes of different wavelength equated in their excitation of either rods or cones. For dim flashes, the pure cone component was similar in waveform to the cone outer segment current, and the rod component was similar to the photovoltage measured directly in rods. With bright flashes, the high frequencies of the rod signal were filtered out by the rod/cone network. The two components of the cone photovoltage adapted separately to background illumination. The amplitude of the rod component was halved by backgrounds eliciting approximately 100 photoisomerizations sec-1 per rod; the cone component was halved by backgrounds of 8700 photoisomerizations sec-1 per cone. Coupling between rods and cones was not modulated by either dim backgrounds or dopamine. Voltage noise in dark-adapted cones was dominated by elementary events other than photopigment isomerizations. The dark noise was equivalent in magnitude to a steady light eliciting approximately 3800 photoisomerizations sec-1 per cone, a value significantly higher than the psychophysical estimates of cone "dark light."     

Circadian rhythms of rod-cone dominance in the Japanese quail retina

When the Japanese quail is held in constant darkness, retinal responses (ERG b-waves) increase during the animal's subjective night and decrease during its subjective day. Rod photoreceptors dominate the b-wave responses (lambdamax = 506 nm) to all stimulus intensities at night but only to those intensities below the cone threshold during the day. Above the cone threshold, cones dominate b-wave responses (lambdamax, approximately 550-600 nm) during the day regardless of the state of retinal adaptation. Apparently a circadian oscillator enables cone signals to block rod signals during the day but not at night. The ERG b-wave reflects the activity of bipolar cells that are postsynaptic to rods and cones. The ERG a-wave reflects the activity of both rods and cones. The amplitude of the isolated a-wave (PIII) changes with time of day, as does that of the b-wave, but its spectral sensitivity does not. The PIII responses are maximal at approximately 520 nm both day and night and may reflect multiple receptor mechanisms. The shift in rod-cone dominance detected with the ERG b-wave resembles the Purkinje shift of human vision but, unlike the Purkinje shift, does not require a change in ambient light intensity. The shift occurs in constant darkness, with a period of approximately 24 hr indicative of a circadian rhythm in the functional organization of the retina.     

Identification and distribution of photoreceptor subtypes in the neotenic tiger salamander retina

The neotenic tiger salamander retina is a major model system for the study of retinal physiology and circuitry, yet there are unresolved issues regarding the organization of the photoreceptors and the photoreceptor mosaic. The rod and cone subtypes in the salamander retina were identified using a combination of morphological and immunocytochemical markers for specific rod and cone opsin epitopes. Because the visual pigment mechanisms present in the tiger salamander retina are well characterized and the antibodies employed in these studies are specific for particular rod and cone opsin epitopes, we also were able to identify the spectral class of the various rod and cone subtypes. Two classes of rods corresponding to the "red" and "green" rods previously reported in amphibian retinas were identified. In serial semithin section analyses, rods and cones comprised 62.4+/-1.4% and 37.6+/-1.4% of all photoreceptors, respectively. One rod type comprising 98.0+/-0.7% of all rods showed the immunological and morphological characteristics of "red" rods, which are maximally sensitive to middle wavelengths. The second rod subtype comprised 2.0+/-0.7% of all rods and possessed the immunological and morphological characteristics of "green" rods, which are maximally sensitive to short wavelengths. By morphology four cone types were identified, showing three distinct immunological signatures. Most cones (84.8+/-1.5% of all cones), including most large single cones, the accessory and principal members of the double cone, and some small single cones, showed immunolabeling by antisera that recognize long wavelength-sensitive cone opsins. A subpopulation of small single cones (8.4+/-1.7% of all cones) showed immunolabeling for short wavelength-sensitive cone opsin. A separate subpopulation of single cones which included both large and small types (6.8+/-1.4% of all cones) was identified as the UV-Cone population and showed immunolabeling by antibodies that recognize rod opsin epitopes. Analysis of flatmounted retinas yielded similar results. All photoreceptor types appeared to be distributed in all retinal regions. There was no obvious crystalline organization of the various photoreceptor subtypes in the photoreceptor mosaic.     

Analysis of ERG a-wave amplification and kinetics in terms of the G-protein cascade of phototransduction

PURPOSE: To test rigorously the hypothesis that the a-wave of the electroretinogram (ERG) is proportional to the rod photocurrent by examining the applicability to a-waves of a recent model of the activation steps in the G-protein cascade of phototransduction. METHODS: ERGs were recorded in response to flashes of graded intensity, from six dark-adapted normal subjects and from two patients, one with retinitis pigmentosa (RP) and one with cone retinal dystrophy with rod involvement (CRD). The a-wave portions of the responses were analyzed with a model of the activation steps of the G-protein cascade. The model is characterized by a parameter, A, the amplification constant, with units of s-2 (per photoisomerization), which may be expressed as the product of physical and biochemical parameters of the transduction cascade. RESULTS: Each a-wave family was well described by the model. For the six normal subjects, we obtained A approximately 7 s-2, about 100-fold greater than in isolated amphibian rods at 22 degrees C, but close to the value for isolated primate rods. For the patient with RP, the maximum a-wave amplitude (amax) was considerably reduced, but the amplification constant was normal (A = 7.5 s-2). In contrast, the patient with CRD had a nearly normal amax but had an amplification constant about sixfold lower than normal (A = 1.1 s-2). CONCLUSIONS: The authors conclude that the a-wave is a direct reflection of the rod photo-current and that the rising phase kinetics are accurately described by a simple model of the G-protein cascade. They show that the small volume of the human rod outer segment is crucial to the achievement of high amplification, and they show how their observations constrain the possible pathologies of phototransduction in patients with retinal disease.     

Recording the oscillatory potentials of the electroretinogram with the DTL electrode

Suprathreshold photopic oscillatory potentials recorded with a DTL electrode were compared to those obtained with a Lovac corneal electrode. The overall oscillatory potential response (sum of oscillatory potentials) recorded with the DTL electrode was half of that obtained with the Lovac electrode. However, there was no evidence of a selective attenuation (or amplification) of any given oscillatory potential with the DTL electrode. Similarly, the oscillatory potential relative amplitude ratios and the peak times of the oscillatory potentials were identical for both electrodes. Our findings clearly indicate that the DTL electrode is adequate to record the high-frequency oscillatory potentials. Given the low cost and ease of use, as well as the disposable nature of the DTL electrode, we believe that electroretinographic specialists should seriously consider a wider utilization.     

Phototransduction: modeling the primate cone flash response

We have developed a new model of phototransduction that accounts for the dynamics of primate and human cone flash responses in both their linear and saturating range. The model incorporates many of the known elements of the phototransduction cascade in vertebrate photoreceptors. The input stage is a new analytic expression for the activation and inactivation of cGMP-phosphodiesterase (PDE). Although the Lamb and Pugh (1992) model (of a delayed ramp for the rising phase of the PDE response in amphibian rods) provided a good fit for the first 2 log units of stimulus intensity without parameter adjustments, the remaining 4 log units of the data required nonlinear modifications of both delay and gain (slope). We show that this nonlinear behavior is a consequence of the delay approximation and develop a completely linear model to account for the rising phase of amphibian rod photocurrent responses over the full intensity range (approximately 6 log units). We use the same dynamic model to account for primate cone responses by decreasing the time constants of PDE activation and introducing an enhanced inactivation process. This PDE response activates a nonlinear calcium feedback stage that modulates guanylate cyclase synthesis of cyclic GMP. By adjustment of the throughput and feedback parameters, the full model successfully captures most of the features of the primate and human cone flash responses throughout their dynamic range. Our analysis suggests that initial processes in the transduction cascade may be qualitatively different from comparable processes in rods.     

Sequential genesis and determination of cone and rod photoreceptors in Xenopus

In this study, we addressed the temporal sequence of photoreceptor fate determination in Xenopus laevis by examining a number of key events during early cone and rod development. We compared the relative timing and spatial pattern of cone and rod specification using a number of cell type-specific markers, including probes to a long wavelength-sensitive opsin which is expressed by the major cone subtype. Our results show that cones are initially more numerous, and can arise in less mature regions of the retina than rods, although both types of photoreceptors begin to express their respective opsins at about the same time. We applied these markers to an assay of cellular determination to identify the stages of embryonic development at which the earliest photoreceptor fates are induced in vivo. The relative birth order of the major cone and rod subtypes was revealed by simultaneous labeling with markers of cell proliferation and terminal differentiation. Although there is much temporal overlap between the periods of cone and rod genesis and determination in Xenopus, we could discern that the earliest cones are both born and determined before the first rods. Thus, even in the rapidly developing retina of Xenopus, photoreceptors achieve their identities in a sequential fashion, suggesting that the inductive cues which determine specific photoreceptor fates may also arise sequentially during development.     

Functional characteristics of lateral interactions between rods in the retina of the snapping turtle

1. Intracellular recordings were made of the slow hyperpolarizing light responses of single rods in the retina of the snapping turtle. Physiological criteria used to identify rods were verified by intracellular injections of Procion Yellow. 2. The amplitudes of the responses elicited by fixed intensity flashes increased as the stimulus was enlarged to a diameter of 300 mum. Scattered light was found incapable of accounting for this effect, which must result from summative interaction of rods with neighbouring receptors. Effects of summative interaction were observed even at stimulus intensities that produced maximal responses. Enlarging the diameter of the higher intensity stimuli from 100 to 300 mum increased the peak response amplitude by almost 50%; it also produced a distinct initial peak of the response which we term overshoot. The amplitude of this overshoot was graded with stimulus size. 3. Complete intensity-response relationships were determined using stimulus diameters of 100 and 750 mum for each rod. With the smaller stimulus the intensity response range was 4-5 log units, and with the larger stimulus this was increased to 5-0 log units. For intensities below about 60 quanta/mum2 per flash (514 nm) the amplitudes elicited by the large stimulus followed a sigmoid-shaped curve. However, at higher intensities an additional lobe appeared on the intensity-response relationship. The appearance of this lobe correlated with the emergence of the overshoot on the response wave form. 4. Determinations of rod flash sensitivity (mV per quantum per mum2) showed that it increased with stimulus size up to a stimulus diameter of about 300 mum. With diameters between 50 and 150 mum, a linear relationship existed between the flash sensitivity and stimulus area. Absolute quantal sensitivities increased with stimulus area by a factor of 26, from a value of 28 muV per photoisomerization per rod with a stimulus 25 mum in diameter, to 720 muV per photoisomerization per rod with a stimulus 300 mum in diameter. 5. By comparison, red-sensitive cones showed increased sensitivity as a function of stimulus size only up to a stimulus diameter of 120 mum. Their over-all sensitivity was lower than that of rods and proved linear with stimulus diameter rather than with stimulus area. 6. Simultaneous recordings were made from rod-cone pairs to determine whether the overshoot, and hence the lobe on the amplitude-intensity function, could result from a cone input to the rod response. The time course of the cone response proved much too rapid to fit the overshoot of the rod response. 7. The spectral sensitivity of the dark-adapted rod response closely followed the difference spectrum of the rod photopigment for wave-lengths greater than 450 nm. This was true throughout the intensity range of the response, including low intensities where response averaging was necessary. 8. At low response amplitudes (approximately 1 mV), about 70% of the 40 rods tested showed responses to long wave-length stimuli consisting of two components...     

Photoreceptor loss in age-related macular degeneration

PURPOSE: The authors showed previously that parafoveal rods, but not cones, decrease during the course of adulthood in donor eyes that were screened to exclude the grossly visible macular drusen and pigmentary disturbances typical of age-related macular degeneration (AMD). Because AMD begins in the parafovea, this selective loss of rods actually may be subclinical AMD not yet visible in the fundus. If so, AMD must have a predilection for rods over cones. The authors tested this hypothesis by determining the relative numbers of cones and rods in donor eyes with mid-to late-stage AMD and in age-matched controls. METHODS: Thirteen eyes (from seven donors) with grossly visible macular drusen and pigmentary disturbances were either wholemounted for photoreceptor counts or sectioned through the fovea for histopathology and carbonic anhydrase histochemistry to label red-green cones. Eyes were assigned to AMD or control groups on the basis of histopathology and clinical history. RESULTS: Five nonexudative AMD (NE-AMD) eyes from three donors showed sparing of foveal cones and loss of rods and cones in the parafovea. In two donors, rod loss exceeded cone loss at most parafoveal locations, and in one donor, rod density was normal and cone density was reduced. In eight exudative AMD (EX-AMD) eyes from five donors, photoreceptors surviving along the margins of and overlying disciform scars were largely cones. CONCLUSIONS: Photoreceptors are lost in NE-AMD as well as in the more severe exudative form, consistent with functional and clinical studies. The authors propose that rods die in older eyes without evidence of overt retinal pigment epithelial disease. In persons susceptible to AMD, the retinal pigment epithelium becomes dysfunctional. Secondarily, rod loss continues and cones begin to degenerate. Eventually, only degenerate cones remain; ultimately, all photoreceptors may disappear.     

A novel signaling pathway from rod photoreceptors to ganglion cells in mammalian retina

Current understanding suggests that mammalian rod photoreceptors connect only to an ON-type bipolar cell. This rod-specific bipolar cell excites the All amacrine cell, which makes connections to cone-specific bipolar cells of both ON and OFF type; these, in turn, synapse with ganglion cells. Recent work on rabbit retina has shown that rod signals can also reach ganglion cells without passing through the rod bipolar cell. This route was thought to be provided by electrical gap junctions, through which rods signal directly to cones and thence to cone bipolar cells. Here, we show that the mouse retina also provides a rod pathway bypassing the rod bipolar cell, suggesting that this is a common feature in mammals. However, this alternative pathway does not require cone photoreceptors; it is perfectly intact in a transgenic mouse whose retina lacks cones. Instead, the results can be explained if rods connect directly to OFF bipolar cells.     

High expression levels in cones of RGS9, the predominant GTPase accelerating protein of rods

RGS9 is a member of the RGS family of GTPase accelerating proteins (GAPs) for heterotrimeric G proteins. We have explored its contribution to GTPase acceleration in mammalian rod and cone photoreceptors. When RGS9 was specifically removed from detergent extracts of rod outer segments by immunodepletion, the extracts lost nearly all of their GAP activity stimulatable by the inhibitory subunit of cGMP phosphodiesterase. Immunolocalization using monoclonal antibodies and confocal microscopy revealed that RGS9 is present in cones at significantly higher levels than in rods. Thus, RGS9 is the predominant source of GAP activity in rod outer segments, and RGS9 concentration emerges as a potentially important determinant of the faster response kinetics and lower sensitivity of mammalian cones, as compared with rods.     

Rod plateaux during dark adaptation in Sorsby's fundus dystrophy and vitamin A deficiency

PURPOSE: To investigate the transitory plateaux observed during dark adaptation after partial bleaches in Sorsby's fundus dystrophy (SFD) and in systemic vitamin A deficiency (VAD). METHODS: Psychophysical dark adaptation functions were measured after bleaching exposures isomerizing from 2% to 99% of the rhodopsin. Narrow-band stimuli of 1.7 degrees diameter and 200 msec duration were presented at an eccentricity of 30 degrees. RESULTS: After a full bleach, the patients showed typical dark adaptation abnormalities reported for these diseases. The cone recovery was slowed, and the time to the rod-cone break was delayed; the final phase of rod recovery was also slowed but led to a normal final rod threshold. After partial bleaches, short wavelength stimuli produced a biphasic recovery function, with an initial rapid component and plateau, followed by a subsequent break-off and eventual return to prebleach thresholds. Action spectra obtained during the plateaux were consistent with thresholds for shorter wavelength stimuli mediated by rods and thresholds for longer wavelength stimuli mediated by cones. In the patient with VAD, vitamin A supplementation led to accelerated recovery and disappearance of the transitory rod plateaux. CONCLUSIONS: The biphasic dark adaptation functions resulting from fractional bleaches in SFD and VAD appear superficially similar to the classic biphasic adaptation functions obtained with full bleaches. However, thresholds during the plateaux are lower than the cone threshold, and action spectra indicate rod mediation. These transitory rod plateaux may increase our understanding of the normal visual cycle and its perturbation in retinal disease.     

Evidence for photoreceptor changes in patients with diabetic retinopathy

PURPOSE: To determine whether the rod and cone photoreceptors are affected in patients with diabetic retinopathy. METHODS: Twelve patients with diabetes and varying levels of retinopathy and nine age-similar control observers participated in this study. Two-color (500 versus 650 nm) dark-adapted thresholds were measured as a function of retinal eccentricity. Full-field flash electroretinograms were obtained using brief, high-intensity flashes. Dark-adapted rod-isolated (Wratten 47B filter) and light-adapted cone-isolated (Wratten 26 filter) electroretinographic responses were measured as a function of flash intensity. The a-wave data were fitted with a model based on photopigment transduction to obtain values for the parameters of Rmax (the maximal response) and log S (sensitivity). Standard clinical 30-Hz flicker electroretinographic responses were also measured. RESULTS: Psychophysically measured dark-adapted thresholds were elevated primarily at eccentricities of 5 degrees and 10 degrees from the fovea. Analysis of rod and cone a-wave data showed that Rmax was normal in most of the patients, but log S was reduced. Analysis of b-wave and oscillatory potential parameters showed rod and cone postreceptoral abnormalities, including changes in the rod-isolated semisaturation constant (log k), cone-mediated 30-Hz flicker, and cone-isolated oscillatory potentials. The electrophysiological results were not significantly correlated with blood glucose or glycosylated hemoglobin level. CONCLUSIONS: The results provide evidence for rod and cone receptoral and postreceptoral deficits in patients with diabetic retinopathy. The photoreceptor changes are primarily in the log S (sensitivity) parameter and are attributed to transduction abnormalities.     

Internal recording of the early receptor potential in turtle cones

1. Early receptor potentials (E.R.P.s) were recorded with internal electrodes in turtle cones by applying brief flashes from a xenon tube with a maximum photon density equivalent to 2-3 x 10(8) photons micronm-2 at the optimum wave-length. 2. The E.R.P. was separated from the late receptor potential (L.R.P.) by superposing in flash on a step of light which was strong enough to saturate the L.R.P. 3. In red-sensitive cones the E.R.P. consisted of a brief depolarizing phase (R1) followed by a hyperpolarizing phase (R2) of maximum amplitude 10 mV and duration 30-40 msec. R1 was small or absent in green-sensitive cones. 4. With flashes of increasing intensity the E.R.P. approached its maximum exponentially with an exponential constant Q of about 10(8) photons micronm-2 which is of the same order as the reciprocal of the photosensitivity of porphyropsin; the implication of this result, which is considered in the theoretical section, is the the E.R.P. is proportional to the number of photoisomerizations. 5. When tested with a constant xenon flash at varying times after the beginning of a bleaching light the E.R.P. declined exponentially with a similar value of Q. 6. After prolonged bleaches the E.R.P. recovered with a time constant of about 100 sec but much quicker recoveries were observed after relatively brief bleaches. 7. The form and size of the E.R.P. are consistent with the accepted view that it arises from a redistribution of charge in the cone pigment molecule. 8. The effect of a single photoisomerization in an isolated cone was estimated as about 10(-10) V or one electronic charge through about 10% of the membrane.     

Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man

Mutations in the gene encoding rhodopsin, the visual pigment in rod photoreceptors, lead to retinal degeneration in species from Drosophila to man. The pathogenic sequence from rod cell-specific mutation to degeneration of rods and cones remains unclear. To understand the disease process in man, we studied heterozygotes with 18 different rhodopsin gene mutations by using noninvasive tests of rod and cone function and retinal histopathology. Two classes of disease expression were found, and there was allele-specificity. Class A mutants lead to severely abnormal rod function across the retina early in life; topography of residual cone function parallels cone cell density. Class B mutants are compatible with normal rods in adult life in some retinal regions or throughout the retina, and there is a slow stereotypical disease sequence. Disease manifests as a loss of rod photoreceptor outer segments, not singly but in microscopic patches that coalesce into larger irregular areas of degeneration. Cone outer segment function remains normal until >75% of rod outer segments are lost. The topography of cone loss coincides with that of rod loss. Most class B mutants show an inferior-nasal to superior-temporal retinal gradient of disease vulnerability associated with visual cycle abnormalities. Class A mutant alleles behave as if cytotoxic; class B mutants can be relatively innocuous and epigenetic factors may play a major role in the retinal degeneration.     

Spatial and temporal expression of cone opsins during monkey retinal development

The primate retina requires a coordinated series of developmental events to form its specialized photoreceptor topography. In this study, the temporal expression of cone photoreceptor opsin was determined in Macaca monkey retina. Markers for mRNA and protein that recognize short wavelength (S) and long/medium wavelength (L/M) opsin were used to determine (1) the temporal and spatial patterns of opsin expression, (2) the spatial relationship between S and L/M cones at the time of initial opsin expression, and (3) the relative time of cone and rod opsin expression (Dorn et al. [1995] Invest. Ophthalmol. Vis. Sci. 36:2634-2651). Adult cone outer segments were recognized by either L/M or S opsin antiserum. Of all adult cone inner segments, 88-90% contained L/M opsin mRNA, whereas 10-12% contained S opsin mRNA. Fetal cones initially showed cell membrane as well as outer segment labeling for opsin protein, but cell membrane labeling disappeared by birth. No cones at any age contained markers for both S and L/M opsin mRNA or protein. S and L/M opsin protein appeared in the fovea at fetal day 75. Once opsin expression progressed beyond the fovea, both mRNA and protein for S opsin were consistently detected more peripherally than L/M opsin. Cones at the peripheral edge of S opsin expression had basal telodendria that appeared to reach toward neighboring cones. Because interactions between cone populations could organize the cone mosaic, the spatial relationship between S cones and the first cones to express L/M protein was analyzed quantitatively by using double-label immunocytochemistry. No consistent relationship was found between these two cone populations. Cones are generated at least 1 week before rods across monkey retina. However, rod opsin protein appears in and around the fovea at fetal day 66, 1 week before cone opsin protein. This suggests that independent local factors control differentiation in these two photoreceptor populations.     

Defect of cold-sensitive response in calmodulin mutants of Paramecium and the restoration by cyclic nucleotide

In carp (Cyprinus) and goldfish (Carassius), long-wavelength cones are reported to be active under scotopic conditions. Using the electroretinogram (ERG), we tested another cyprinid fish, Danio aequipinnatus, which contains A1-based visual pigments and for which we had previously measured the spectral sensitivities of individual cones. Dark adaptation curves show a rod/cone break at about 45 min. When thoroughly dark-adapted, the spectral sensitivity function is broader than can be accounted for by self-screening of rhodopsin, but it can be modeled by an additive combination of rods and the 560-nm cones. Dim, red background light causes adaptation of rods and a broadening of the spectral sensitivity function, which can be simulated by increasing the proportion of cones in the model. Brighter red backgrounds adapt the 560-nm cones. Because of the effect of red adapting lights, the ERG evidence for the participation of long-wavelength cones close to visual threshold appears to be different in Danio than in the goldfish Carassius.     

Retinal photoreceptor density decreases with age

PURPOSE: To evaluate the effect of age on the density of retinal photoreceptors in humans. METHODS: Fifty-five normal eyes from human donors, with a mean age of 58.7 +/- 19.1 years and an axial length of less than 27 mm, were examined. After opening of the globes by a 16-mm corneoscleral trephination, 25 retinal tissue samples were obtained in four meridians. The photoreceptors were counted on photographs taken from the photoreceptor inner segments after sonographic removal of the outer segments. The cones in the foveal center could not be evaluated. RESULTS: Outside the foveal center, the photoreceptor density decreased significantly with increasing age. In absolute and relative terms, the decline was more marked for the rods (mean rod loss, 236 +/- 63 cells or 0.37% +/- 0.10%/mm2 and year of a mean density of 62.987 rods/mm2) than for the cones (mean cone loss, 5.90 +/- 0.68 cells or 0.18% +/- 0.02%/mm2 and year of a mean density of 3320 +/- 578 cones/mm2). For both cones and rods, the cell loss was more marked at an eccentricity of approximately 5-8 mm than in the retinal periphery at an eccentricity of 14 to 20 mm. There were no significant differences between the superior, inferior, temporal, or nasal meridian nor between women and men. CONCLUSIONS: The photoreceptors decrease in density with increasing age. The annual cell loss of approximately 0.2% to 0.4% is similar to the age-related loss of retinal ganglion cells and pigment epithelium cells. The decline in photoreceptor count affects more rods than cones. It does not prefer special age groups. It is more pronounced at an eccentricity of 5 to 8 mm than in the retinal periphery at an eccentricity of more than 14 mm. It may be important for an age-related decrease in visual functions and for diseases affecting the photoreceptors in elderly patients.     

Retinal and lenticular ultrastructure in the aestivating salamanderfish, Lepidogalaxias salamandroides (Galaxiidae, Teleostei) with special reference to a new type of photoreceptor mosaic

The salamanderfish, Lepidogalaxias salamandroides (Galaxiidae, Teleostei) is endemic to southwestern Australia and inhabits shallow, freshwater pools which evaporate during the hot summer months. Burrowing into the substrate in response to falling water levels allows these fish to aestivate for extended periods of time while encapsulated in a mucous cocoon even when the pools contain no water. Only a few minutes after a major rainfall, these fish emerge into relatively clear water which subsequently becomes laden with tannin, turning the water black and reducing the pH to approximately 4.3. As part of a large study of the visual adaptations of this unique species, the retinal and lenticular morphology of the aestivating salamanderfish is examined at the level of the light and electron microscopes. The inner retina is highly vascularised by a complex system of vitreal blood vessels, while the outer retina receives a blood supply by diffusion from a choriocapillaris. This increased retinal blood supply may be an adaptation for reducing the oxygen tension during critical periods of aestivation. Large numbers of Müller cells traverse the thickness of the retina from the inner to the outer limiting membranes. The ganglion cells are arranged in two ill-defined layers, separated from a thick inner nuclear layer containing two layers of horizontal cells by a soma-free inner plexiform layer. The photoreceptors can be divided into three types typical of many early actinopterygian representatives; equal double cones, small single cones and large rods (2:1:1). These photoreceptors are arranged into a unique regular square mosaic comprising a large rod bordered by four equal double cones with a small single cone located at the corner of each repeating unit. The double cones may optimise perception of mobile prey which it tracks by flexion of its head and "neck" and the large rods may increase sensitivity in the dark tannin-rich waters in which it lives. Each single cone also possesses a dense collection of polysomes and glycogen (a paraboloid) beneath its ellipsoid, the first such finding in teleosts. The retinal pigment epithelium possesses melanosomes, phagocytes and a large number of mitochondria. The anatomy of the retina and the photoreceptor mosaic is discussed in relation to the primitive phylogeny of this species and its unique life history.     

UV- and midwave-sensitive cone-driven retinal responses of the mouse: a possible phenotype for coexpression of cone photopigments

Molecular biological, histological and flicker electroretinographic results have established that mice have two cone photopigments, one peaking near 350 nm (UV-cone pigment) and a second near 510 nm [midwave (M)-cone pigment]. The goal of this investigation was to measure the action spectra and absolute sensitivities of the UV-cone- and M-cone-driven b-wave responses of C57BL/6 mice. To achieve this goal, we suppressed rod-driven signals with steady or flashed backgrounds and obtained intensity-response relations for cone-driven b-waves elicited by narrowband flashes between 340 and 600 nm. The derived cone action spectra can be described as retinal1 pigments with peaks at 355 and 508 nm. The UV peak had an absolute sensitivity of approximately 8 nV/(photon microm2) at the cornea, approximately fourfold higher than the M peak. In an attempt to isolate UV-cone-driven responses, it was discovered that an orange conditioning flash (lambda > 530 nm) completely suppressed ERG signals driven by both M pigment- and UV pigment-containing cones. Analysis showed that the orange flash could not have produced a detectable response in the UV-cone pathway were their no linkage between M pigment- and UV pigment-generated signals. Because cones containing predominantly the UV and M pigments have been shown to be located largely in separate parts of the mouse retina (), the most probable linkage is coexpression of M pigment in cones primarily expressing UV pigment. New histological evidence supports this interpretation (). Our data are consistent with an upper bound of approximately 3% coexpression of M pigment in the cones that express mostly the UV pigment.