Photoreceptor Cell Density Research Articles

The correlation of caspase-3 expression with retinal ganglion and photoreceptor cell densities in diabetic retinopathy

The correlation of caspase-3 expression with retinal ganglion and photoreceptor cell densities in diabetic retinopathy

Inhibition of NLRP3 inflammasome by MCC950 under hypoxia alleviates photoreceptor apoptosis via inducing autophagy in Müller glia.

NLRP3 inflammasome activation has emerged as a critical initiator of inflammatory response in ischemic retinopathy. Here, we identified the effect of a potent, selective NLRP3 inhibitor, MCC950, on autophagy and apoptosis under hypoxia. Neonatal mice were exposed to hyperoxia for 5 days to establish oxygen-induced retinopathy (OIR) model. Intravitreal injection of MCC950 was given, and then autophagy and apoptosis markers were assessed. Retinal autophagy, apoptosis, and related pathways were evaluated by western blot, immunofluorescent labeling, transmission electron microscopy, and TUNEL assay. Autophagic activity in Müller glia after NLRP3 inflammasome inhibition, together with its influence on photoreceptor death, was studied using western blot, immunofluorescence staining, mRFP-GFP-LC3 adenovirus transfection, cell viability, proliferation, and apoptosis assays. Results showed that activation of NLRP3 inflammasome in Müller glia was detected in OIR model. MCC950 could improve impaired retinal autophagic flux and attenuate retinal apoptosis while it regulated the retinal AMPK/mTOR/ULK-1 pathway. Suppressed autophagy and depressed proliferation capacity resulting from hypoxia was promoted after MCC950 treatment in Müller glia. Inhibition of AMPK and ULK-1 pathway significantly interfered with the MCC950-induced autophagy activity, indicating MCC950 positively modulated autophagy through AMPK/mTOR/ULK-1 pathway in Müller cells. Furthermore, blockage of autophagy in Müller glia significantly induced apoptosis in the cocultured 661W photoreceptor cells, whereas MCC950 markedly preserved the density of photoreceptor cells. These findings substantiated the therapeutic potential of MCC950 against impaired autophagy and subsequent apoptosis under hypoxia. Such protective effect might involve the modulation of AMPK/mTOR/ULK-1 pathway. Targeting NLRP3 inflammasome in Müller glia could be beneficial for photoreceptor survival under hypoxic conditions.

Frequency cumulative effect of subthreshold energy laser-activated remote phosphors irradiation on visual function in guinea pigs.

To explore the effects of laser-activated remote phosphors (LARP) on visual function in guinea pigs. Electroretinogram (ERG) of guinea pigs were observed after LARP irradiation at different frequencies and irradiation times. We evaluated the expression of rhodopsin, β-catenin, connexin36, calretinin, and calbindin in the retina of guinea pigs and measured the density of photoreceptor cells after high-frequency LARP irradiation. After LARP irradiation, the ERG results showed that the amplitude of the dark-adapted 3.0 b-wave of the model eye was lower than that of the control eye after high-frequency irradiation (P<0.05). The expression of rhodopsin, β-catenin, connexin36, calretinin, and calbindin in the retina of guinea pig declined. There is frequency cumulative damage effect on the retina that relates to LARP illumination frequency. This has significance for staff visual protection policies under LARP lighting conditions.

Human Eye Optics within a Non-Euclidian Geometrical Approach and Some Implications in Vision Prosthetics Design.

An analogy with our previously published theory on the ionospheric auroral gyroscope provides a new perspective in human eye optics. Based on cone cells’ real distribution, we model the human eye macula as a pseudospherical surface. This allows the rigorous description of the photoreceptor cell densities in the parafoveal zones modeled further by an optimized paving method. The hexagonal photoreceptors’ distribution has been optimally projected on the elliptical pseudosphere, thus designing a prosthetic array counting almost 7000 pixel points. Thanks to the high morphological similarities to a normal human retina, the visual prosthesis performance in camera-free systems might be significantly improved.

Automated Cone Photoreceptor Cell Segmentation and Identification in Adaptive Optics Scanning Laser Ophthalmoscope Images Using Morphological Processing and Watershed Algorithm

Geometrical analysis of cone photoreceptor cells is important not only for ophthalmic diagnosis, but also for research on eye diseases. In this study, an automated cone photoreceptor cell segmentation and identification method based on morphological processing and watershed algorithm is presented for adaptive optics scanning laser ophthalmoscope images. Our method includes steps for image denoising, rough segmentation, fine segmentation, small region removal, and identification. The effectiveness of the proposed method was confirmed by comparing its results with those obtained manually yielding precision, recall, and F1-score values of 93.6%, 98.0% and 95.8%, respectively. The performance of our method is further verified by processing images with different cone photoreceptor cell densities from healthy retina and an image from an eye with diabetic retinopathy. The experimental results show that our algorithm achieved high accuracy in cone photoreceptor cell segmentation and identification in healthy retinas as well as in retina with diabetic retinopathy.

The effects of Crumbs proteins on zebrafish photoreceptors

Objective To observe the effects of Crumbs (Crb) proteins on different types of zebrafish photoreceptors. Methods The retinal cell population dynamics of adult wild-type zebrafish and Tg (RH2-2:Crb2b-sf-EX/RH2-2:GFP)pt108b transgenic zebrafish (called pt108b zebrafish for short) were evaluated by monitoring the densities of three categories of retinal photoreceptors (rod cells, UV cone cells and RGB cone cells) in different retinal regions, which were visualized by Feulgen nuclear staining histology technique. Results The wild-type zebrafish retinal photoreceptor cell densities are generally higher in the central region than the peripheral regions. Compared with wild-type zebrafish, pt108b zebrafish had much less RGB cone cells at the top of outer nuclear layer, and no RGB cone cells at the central and intermediate regions of retina. While pt108b zebrafish had normal density of UV cone cells at the top of rods and the bottom of outer limiting membrane, they had much higher density of rods. Conclusions Crb proteins may affect the zebrafish retinal cell densities of different photoreceptor types. Key words: Photoreceptor cells, vertebrate/physiology; Zebrafish; Animal experimentation

MORPHOLOGICAL TYPES AND ARRANGEMENT OF CONE CELLS, AND THE VISUAL ACUITY OF SUTCHI CATFISH PANGASIANODON HYPOPHTHALMUS

The density and spatial arrangement of photoreceptor cells in the retina reflect the visual environment of a fish. The density of photoreceptor cells also determines the visual acuity. In this study, the morphological types and arrangement of cone cells, and the visual acuity of sutchi catfish Pangasianodon hypophthalmus were determined to obtain fundamental understanding of its vision. The left eyes of the adult sutchi catfish were enucleated, fixed in Bouin’s solution for 24 hours and then preserved in 70% ethanol. The fixed retinae were cut into 17 regions. The nine major regions were the dorso-nasal (DN), dorsal (D), dorso-temporal (DT), nasal (N), bottom (B), temporal (T), ventro-nasal (VN), ventral (V), and ventro-temporal (VT). The 17 regions were then immersed separately in a series of ethanol (from 70% to 100%), cleared with histolene, embedded in paraffin, cut into 6 μm thick tangential sections, and stained with haematoxylin-eosin. The density of cone cells per 0.01 mm2 in each region was counted from the stained sections. Visual acuity was then calculated using cone cell densities and lens radii. Only one type of cone cells, which is the single cone cell, was identified and these single cone cells were closely spaced. The area around the bottom region showed tendency of higher density of single cone cells. These findings provide the fundamental understanding on the adaptation of retinal structure of sutchi catfish to its feeding behaviour.

Detection of retinal changes in idiopathic Parkinson's disease using high-resolution optical coherence tomography and heidelberg retina tomography.

The study was performed to analyse the retina of patients with Parkinson's disease (PD) for morphological changes compared to healthy controls (HC) using spectral-domain optical coherence tomography (SD-OCT) and confocal scanning laser ophthalmoscopy. We enrolled 108 patients with idiopathic PD and 165 HC. All study participants underwent an ophthalmological examination to exclude ophthalmological disorder potentially interfering with the retinal analyses. Peripapillary retinal nerve fibre layer (RNFL) thickness and macular thickness and volume were measured by a SD-OCT device (Heidelberg Spectralis(®) ). Stereometric parameters of the optic disc were acquired by Heidelberg Retina Tomograph (HRT III). The RNFL thickness did not significantly differ between patients with PD and HC. The thickness of the central minimum and the centre of the macular area were significantly reduced in patients with PD, while the total macular volume did not significantly differ between the groups. Furthermore, we noted an inverse correlation between the central minimum thickness and the disease severity (assessed by the Hoehn and Yahr scale). HRT data showed no significant differences. The HRT device and the RNFL measurements of the SD-OCT did not prove to be a clinically valid diagnostic tool to distinguish eyes of patients with PD and HC. However, the macular region and especially the foveola (central minimum) with the highest density of photoreceptor cells seem to be more sensitive and might be potential biomarkers.

A comparison of some organizational characteristics of the mouse central retina and the human macula.

Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch’s membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch’s membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.

Retinal imaging using adaptive optics technology

Adaptive optics (AO) is a technology used to improve the performance of optical systems by reducing the effect of wave front distortions. Retinal imaging using AO aims to compensate for higher order aberrations originating from the cornea and the lens by using deformable mirror. The main application of AO retinal imaging has been to assess photoreceptor cell density, spacing, and mosaic regularity in normal and diseased eyes. Apart from photoreceptors, the retinal pigment epithelium, retinal nerve fiber layer, retinal vessel wall and lamina cribrosa can also be visualized with AO technology. Recent interest in AO technology in eye research has resulted in growing number of reports and publications utilizing this technology in both animals and humans. With the availability of first commercially available instruments we are making transformation of AO technology from a research tool to diagnostic instrument. The current challenges include imaging eyes with less than perfect optical media, formation of normative databases for acquired images such as cone mosaics, and the cost of the technology. The opportunities for AO will include more detailed diagnosis with description of some new findings in retinal diseases and glaucoma as well as expansion of AO into clinical trials which has already started.

Moderate Light-Induced Degeneration of Rod Photoreceptors with Delayed Transducin Translocation inshaker1Mice

PURPOSE. Usher syndrome is characterized by congenital deafness associated with retinitis pigmentosa (RP). Mutations in the myosin VIIa gene (MYO7A) cause a common and severe subtype of Usher syndrome (USH1B). Shaker1 mice have mutant MYO7A. They are deaf and have vestibular dysfunction but do not develop photoreceptor degeneration. The goal of this study was to investigate abnormalities of photoreceptors in shaker1 mice. METHODS. Immunocytochemistry and hydroethidine-based detection of intracellular superoxide production were used. Photoreceptor cell densities under various conditions of light/dark exposures were evaluated. RESULTS. In shaker1 mice, the rod transducin translocation is delayed because of a shift of its light activation threshold to a higher level. Even moderate light exposure can induce oxidative damage and significant rod degeneration in shaker1 mice. Shaker1 mice reared under a moderate light/dark cycle develop severe retinal degeneration in less than 6 months. CONCLUSIONS. These findings show that, contrary to earlier studies, shaker1 mice possess a robust retinal phenotype that may link to defective rod protein translocation. Importantly, USH1B animal models are likely vulnerable to light-induced photoreceptor damage, even under moderate light.

An empty E1−, E3−, E4− adenovirus vector protects photoreceptors from light-induced degeneration

We have previously identified a neuroprotective effect associated with empty (E1−, E3−, E4−) adenovirus vector delivery in a model of light-induced, photoreceptor cell death. In this study, we further characterize this protective effect in light-injured retina and investigate its molecular basis. Dark-adapted BALB/c mice, aged 6–8 weeks, were exposed to standardized, intense fluorescent light for 96 or 144 h. Prior to dark adaptation, all mice received intravitreous injection of 1 × 109 particles of an empty (E1−, E3−, E4−) adenovirus vector in one eye and vehicle in the other. Following light challenge of 96 or 144 h, histopathological analysis and quantitative photoreceptor cell counts were conducted. Semiquantitative assessment of messenger ribonucleic acid (mRNA) for the apoptosis related genes: p50, p65, IkBa, caspase-1, caspase-3, Bad, c-Jun, Bax, Bak, Bcl-2, c-Fos, and p53 using quantitative reverse transcriptase polymerase chain reaction was performed on eyes following 12 h of light exposure. Following 96 h of light exposure, the photoreceptor cell density for E1−, E3−, E4− adenovirus vector and vehicle-injected eyes were 87.5 ± 9.5 and 79.3 ± 10.1, respectively, (p = 0.79). After 144 h of light exposure, the photoreceptor cell density was preserved in vector-injected eyes as compared to vehicle treated eyes, 68.9 ± 10.0 and 49.2 ± 4.6, respectively (p = 0.016). Relative mRNA levels of c-Fos and c-Jun at 12-h light exposure after injection differed significantly between vector- and vehicle-injected eyes (p = 0.036, 0.016, respectively). The expression of the other apoptosis-related genes evaluated was not significantly affected. This study investigates the molecular basis of photoreceptor neuroprotective pathway induction associated with E1−, E3−, E4− adenovirus vectors. The results indicate that empty adenovirus vectors protect photoreceptors from light-induced degeneration by the modulation of apoptotic pathways. Gene expression changes suggest that the suppression of c-Fos and c-Jun upregulation contributes significantly to the neuroprotective effect. Understanding the molecular basis of the neuroprotective pathway induction in photoreceptors is critical to the development of novel therapies for retinal degenerations.

Number and density of retinal photoreceptor cells with emphasis on oil droplet distribution in the Mallard Duck (Anas platyrhynchos var. domesticus)

ABSTRACTThis study was intended to determine the number and regional distribution of photoreceptor cells and different colored oil droplets in the retina of the Mallard Duck (Anas platyrhynchos var. domesticus). To estimate the number and density of photoreceptor cells, adult ducks were killed and both eyes were enucleated under deep anesthesia to prepare Nissl‐stained retinal whole‐mount samples. Different colored oil droplets were counted from color microphotographs of the freshly prepared retina. The mean number of retinal photoreceptors was approximately 6 308 828 ± 521 927, with a peak density of 33 573/mm2 in the central retina. The density was similar in the nasal, temporal, ventral and dorsal areas of the retina. Five types of oil droplets were identified on the basis of color: red, orange, greenish‐yellow, yellow and clear. The mean density of oil droplets was highest in the central retina (17 639/mm2) and gradually declined towards the nasal, temporal, ventral and dorsal areas. The size of oil droplets gradually increased with retinal eccentricity and varied even within an area. The greenish‐yellow oil droplets were most abundant across the retina. Taken together, these results demonstrate the differential retinal distribution of photoreceptor cells and oil droplets in duck retina. We conclude that the area of high photoreceptor cell density, which is matched by high neuron densities of the ganglion cell layer, corresponds to the site of acute vision in duck retina.

Topography of retinal photoreceptor cells in the Jungle Crow (Corvus macrorhynchos) with emphasis on the distribution of oil droplets

Previously, we analyzed the regional specialization of ganglion cells in the retina of the Jungle Crow (Corvus macrorhynchos). The present study extends this analysis by determining the numbers and regional distribution of photoreceptor cells and the different colored oil droplets. The numbers of the different colored oil droplets were counted using color microphotographs of fresh retinas. Estimation of the numbers of photoreceptor cells was made using Nissl-stained retinal whole mounts. The estimated total number of photoreceptor cells in the whole mount retina was approximately 17,933,788 (N=4). The peak density of photoreceptor cells was 92,109/mm2 in the central area of the retina, followed by temporal and nasal areas, respectively. Four types of oil droplet were identified on the basis of their color: red, orange, green and translucent. The central retina had a significantly higher population of oil droplets, with a density of 91,202/mm2; this sharply declined at the peripheral retina. The lowest observed density was 13,192/mm2 in the dorsal retina. The densities and sizes of the different colored oil droplets were inversely correlated across the retina. The average sizes of red, orange, green and translucent oil droplets had 6 μm2, 4 μm2, 7 μm2 and 4 μm2, respectively. At the periphery of the retina, the oil droplets were significantly larger than in the central area. The sizes of the different colored oil droplets also varied within the same area. Orange colored oil droplets (33%) were the most common type in the central area, whereas green colored oil droplets were the most frequent in other areas. The results of the present study show that photoreceptor cells and oil droplets are differentially distributed in the retina. From these results, we conclude that the area of high cell density, matched by high neuron densities of the ganglion cell layer, corresponds to the site of acute color vision in the crow retina.

Synaptic Pathology, Altered Gene Expression, and Degeneration in Photoreceptors Impacted by Drusen

Drusen are risk factors for age-related macular degeneration and have been shown to negatively impact cells of the RPE and retina. In this study, the effects of drusen on the synaptic machinery of retinal photoreceptors are investigated. Human donor eye tissue containing retina, RPE, and choroid was processed for confocal immunofluorescence microscopy, laser capture microdissection, and light and electron microscopy. Tissue sections were immunostained with a panel of antibodies to synapse-associated proteins. Populations of photoreceptors over drusen and normal populations of photoreceptors were microdissected from fresh frozen tissue, RNA was purified, and quantitative PCR was performed to compare relative levels of gene expression. The number of photoreceptor synaptic terminals is reduced in regions of the outer plexiform layer over drusen, synaptic proteins are mislocalized in photoreceptor cells, and synaptic terminals are often observed within the outer nuclear layer. Photoreceptors over drusen also increase expression of the stress response proteins apolipoprotein E and alphaB-crystallin. Abnormal immunolabeling patterns are not restricted to photoreceptors directly over drusen but are also observed in cells flanking drusen. Gene expression analysis confirms reductions in the expression of genes coding for synapse-associated proteins and signal transduction proteins and increases in the expression of apolipoprotein E and alphaB-crystallingene transcripts. Ultrastructural analysis of photoreceptor synaptic terminals over drusen reveals significant abnormalities, and cell counts show a reduction in photoreceptor density directly over, and lateral to, drusen of all sizes. Photoreceptors overlying and flanking drusen exhibit morphologic and biochemical signs of degeneration. The expression of synapse-associated proteins decreases in photoreceptor synaptic terminals, whereas the expression of stress-response proteins increases. Reductions in photoreceptor cell densities over, and flanking, drusen suggest that these degenerative effects eventually result in the death of photoreceptors.

Intraocular gene transfer of pigment epithelium-derived factor rescues photoreceptors from light-induced cell death.

In this study, we investigated whether intraocular gene transfer of pigment epithelium-derived factor (PEDF) ameliorates the extent of light-induced photoreceptor cell death. Lewis rats received intravitreous injection of 3 x 10(9) particles of adenoviral vector expressing PEDF (AdPEDF.11) in one eye and 3 x 10(9) particles of empty adenoviral vector (AdNull.11) in the contralateral eye. The rats were then dark-adapted for 3 days after which they were continuously exposed to fluorescent light (2,500 lux) for 0, 6, 24, 96, and 168 h. Both eyes were then enucleated and processed for morphometric analysis. Cell death in the retina was examined using TUNEL staining with a propidium iodide counterstain. The photoreceptor cell counts in each of the three groups were significantly different (P < 0.001). Eyes that received intravitreous injection of AdNull.11 or no injection showed a greater number of pyknotic photoreceptor cells and a reduced photoreceptor cell density as compared to eyes treated with intravitreous AdPEDF.11 injection. AdNull.11 treated eyes showed a lesser but still significant protection of photoreceptor cells when compared to untreated eyes. Fewer TUNEL-positive photoreceptor cells were present in AdPEDF.11 treated eyes than in AdNull.11 treated or untreated eyes (P = 0.004). The amplitudes of the ERG a-wave, b-wave, and oscillatory potentials (OPs) were increased significantly by treatment (P < 0.05). These data suggest that adenovirus vector-mediated intraocular expression of PEDF significantly increases photoreceptor cell survival following excessive light exposure. Neuroprotection may result from inhibition of light-induced apoptotic processes. This study provides proof of concept for a gene transfer approach to modulating retinal cell death resulting from photo-oxidative damage and supports the hypothesis that gene transfer of PEDF is broadly applicable to modulating apoptosis in the retina.

Real-time foveation techniques for low bit rate video coding

Lossy video compression methods often rely on modeling the abilities and limitations of the intended receiver, the human visual system (HVS), to achieve the highest possible compression with as little effect on perceived quality as possible. Foveation, which is non-uniform resolution perception of the visual stimulus by the HVS due to the non-uniform density of photoreceptor cells in the eye, has been demonstrated to be useful for reducing bit rates beyond the abilities of uniform resolution video coders. In this work, we present real-time foveation techniques for low bit rate video coding. First, we develop an approximate model for foveation. Then, we demonstrate that foveation, as described by this model, can be incorporated into standard motion compensation and discrete cosine transform (DCT)-based video coding techniques for low bit rate video coding, such as the H.263 or MPEG-4 video coding standards, without incurring prohibitive complexity overhead. We demonstrate that foveation in the DCT domain can actually result in computational speed-ups. The techniques presented can be implemented using the baseline modes in the video coding standards and do not require any modification to, or post-processing at, the decoder.

Age-related changes in the mouse outer retina.

To define the physiological and structural changes that may accompany aging in the normal mouse retina. C57BL/6 mice were maintained under cyclic light for either 2, 6, or 12 months. After rod- and cone-mediated corneal electroretinograms (ERG's) were recorded from anesthetized animals, the retinal structure was quantitatively examined. Photoreceptor cell density was measured within 100-microm regions of the central superior and inferior retina. Cone photoreceptor subtypes were identified by immunocytochemistry. The amplitudes of rod- and cone-mediated ERG's were reduced in older mice, although the overall ERG wave-form did not change appreciably and implicit times were not changed in an age-dependent fashion. In comparison, there was no significant age-related decline in rod or cone photoreceptor density. The amplitude of the mouse ERG declines with age. This change does not appear to reflect a change in the structural integrity of the photoreceptor cells. In functional studies of murine models of late-onset retinal disorders, it will be important to take these changes into consideration.

Calorie restriction increases light-dependent photoreceptor cell loss in the neural retina of Fischer 344 rats

We investigated the effect of ≥8 months of 40% caloric restriction (CR) on photoreceptor cell loss in 12, 18, and 24 month-old Fischer 344 rats ( N = 154). Rats were reared at the NIA Biomarkers Program, National Center for Toxicological Research. Photoreceptor cell density, assessed histologically, declined with age in both the CR-fed and ad lib (AL)-fed cohorts ( P < 0.000), but declines were more pronounced in the CR cohort ( P < 0.0005). The deleterious effect of CR was most pronounced in the central as opposed to the peripheral retina ( P = 0.008), suggesting a light-dependent mechanism. Photoreceptor cell density was inversely associated with rearing under bright light (300–750 lux) as compared with rearing under lower illuminance (≤200 lux) ( P < 0.0005). However, the deleterious effect of bright light on photoreceptor cell density was more pronounced in the CR cohort ( P = 0.04). Effects of CR on circadian activity are likely to increase the actual light exposure of the CR cohort and may explain the apparent inability of CR to delay retinal aging in albino rats.

Anatomical correlates of experimentally induced myopia.

The present study compares morphological changes associated with optical defocus-induced myopia (ODM) with those from form deprivation myopia (FDM), as it is yet to be determined whether the latter is a consequence of visual deprivation or active myopic eye growth. Hatchling chicks were reared for 2 weeks wearing a monocular translucent occluder or -10.00 D lens, with the other eye used as a control. After enucleation, eyes were processed for scanning electron microscopy. Anatomical profiles of control eyes revealed significant variations in tissue thickness as a function of nasotemporal location. Both FDM and ODM eyes demonstrated similar morphological profiles of retinal thinning, cartilaginous scleral thickening, enlarged photoreceptor inner segments and decreased photoreceptor cell density towards the ora serrata. A graded differential orientation of photoreceptors existed in all eyes. The comparable morphological changes in FDM and ODM suggest that the response to altered visual experience is similar in both paradigms.