Photoreceptor Signals Research Articles

Drosophila Vision Depends on Carcinine Uptake by an Organic Cation Transporter.

Recycling of neurotransmitters is essential for sustained neuronal signaling, yet recycling pathways for various transmitters, including histamine, remain poorly understood. In the first visual ganglion (lamina) of Drosophila, photoreceptor-released histamine is taken up into perisynaptic glia, converted to carcinine, and delivered back to the photoreceptor for histamine regeneration. Here, we identify an organic cation transporter, CarT (carcinine transporter), that transports carcinine into photoreceptors during histamine recycling. CarT mediated in vitro uptake of carcinine. Deletion of the CarT gene caused an accumulation of carcinine in laminar glia accompanied by a reduction in histamine, resulting in abolished photoreceptor signal transmission and blindness in behavioral assays. These defects were rescued by expression of CarT cDNA in photoreceptors, and they were reproduced by photoreceptor-specific CarT knockdown. Our findings suggest a common role for the conserved family of CarT-like transporters in maintaining histamine homeostasis in both mammalian and fly brains.

Visual ecology and potassium conductances of insect photoreceptors.

Voltage-activated potassium channels (Kv channels) in the microvillar photoreceptors of arthropods are responsible for repolarization and regulation of photoreceptor signaling bandwidth. On the basis of analyzing Kv channels in dipteran flies, it was suggested that diurnal, rapidly flying insects predominantly express sustained K(+) conductances, whereas crepuscular and nocturnally active animals exhibit strongly inactivating Kv conductances. The latter was suggested to function for minimizing cellular energy consumption. In this study we further explore the evolutionary adaptations of the photoreceptor channelome to visual ecology and behavior by comparing K(+) conductances in 15 phylogenetically diverse insects, using patch-clamp recordings from dissociated ommatidia. We show that rapid diurnal flyers such as the blowfly (Calliphora vicina) and the honeybee (Apis mellifera) express relatively large noninactivating Kv conductances, conforming to the earlier hypothesis in Diptera. Nocturnal and/or slow-moving species do not in general exhibit stronger Kv conductance inactivation in the physiological membrane voltage range, but the photoreceptors in species that are known to rely more on vision behaviorally had higher densities of sustained Kv conductances than photoreceptors of less visually guided species. No statistically significant trends related to visual performance could be identified for the rapidly inactivating Kv conductances. Counterintuitively, strong negative correlations were observed between photoreceptor capacitance and specific membrane conductance for both sustained and inactivating fractions of Kv conductance, suggesting insignificant evolutionary pressure to offset negative effects of high capacitance on membrane filtering with increased conductance.

Signalling beyond photon absorption: extracellular retinoids and growth factors modulate rod photoreceptor sensitivity.

We propose that the end product of chromophore bleaching in rod photoreceptors, all-trans retinol, is part of a feedback loop that increases the sensitivity of the phototransduction cascade in rods. A previously described light-induced hypersensitivity in rods, termed adaptive potentiation, is reduced by exogenously applied all-trans retinol but not all-trans retinal. This potentiation is produced by insulin-like growth factor-1, whose binding proteins are located in the extracellular matrix, even in our isolated retina preparation after removal of the retinal pigmented epithelium. Simple modelling suggests that the light stimuli used in the present study will produce sufficient all-trans retinol within the interphotoreceptor matrix to explain the potentiation effect. Photoreceptors translate the absorption of photons into electrical signals for propagation through the visual system. Mammalian photoreceptor signalling has largely been studied in isolated cells, and such studies have necessarily avoided the complex environment of supportive proteins that surround the photoreceptors. The interphotoreceptor matrix (IPM) contains an array of proteins that aid in both structural maintenance and cellular homeostasis, including chromophore turnover. In signalling photon absorption, the chromophore 11-cis retinal is first isomerized to all-trans retinal, followed by conversion to all-trans retinol (ROL) for removal from the photoreceptor. Interphotoreceptor retinoid-binding protein (IRBP) is the most abundant protein in the IPM, and it promotes the removal of bleached chromophores and recycling in the nearby retinal pigment epithelium. By studying the light responses of isolated mouse retinas, we demonstrate that ROL can act as a feedback signal onto photoreceptors that influences the sensitivity of phototransduction. In addition to IRBP, the IPM also contains insulin-like growth factor-1 (IGF-1) and its associated binding proteins, although their functions have not yet been described. We demonstrate that extracellular application of physiological concentrations of IGF-1 can increase rod photoreceptor sensitivity in mammalian retinas. We also determine that chromophores and growth factors can limit the range of a newly described form of photoreceptor light adaptation. Finally, fluorescent antibodies demonstrate the presence of IRBP and IGFBP-3 in isolated retinas. A simple model of the formation and release of ROL into the extracellular space quantitatively describes this novel feedback loop.

Blue light-induced LOV domain dimerization enhances the affinity of Aureochrome 1a for its target DNA sequence.

The design of synthetic optogenetic tools that allow precise spatiotemporal control of biological processes previously inaccessible to optogenetic control has developed rapidly over the last years. Rational design of such tools requires detailed knowledge of allosteric light signaling in natural photoreceptors. To understand allosteric communication between sensor and effector domains, characterization of all relevant signaling states is required. Here, we describe the mechanism of light-dependent DNA binding of the light-oxygen-voltage (LOV) transcription factor Aureochrome 1a from Phaeodactylum tricornutum (PtAu1a) and present crystal structures of a dark state LOV monomer and a fully light-adapted LOV dimer. In combination with hydrogen/deuterium-exchange, solution scattering data and DNA-binding experiments, our studies reveal a light-sensitive interaction between the LOV and basic region leucine zipper DNA-binding domain that together with LOV dimerization results in modulation of the DNA affinity of PtAu1a. We discuss the implications of these results for the design of synthetic LOV-based photosensors with application in optogenetics.

Four photoreceptor classes in the open rhabdom eye of the red palm weevil, Rynchophorus ferrugineus Olivier.

The red palm weevil (RPW) is a severe palm pest with high dispersal capability. Its visual sense allows it to navigate long distances and to discriminate among differently colored traps. We investigated the RPW compound eyes with anatomical and electrophysiological methods. The ommatidia are composed of eight photoreceptor cells in an open rhabdom arrangement with six peripheral and two central photoreceptors. The photoreceptor signals are relatively slow and noisy. The majority of recorded photoreceptors have broad spectral sensitivity with a peak in the green, at 536 nm. Three minor classes of photoreceptors have narrower spectral sensitivities with maxima in the UV (366 nm), green (520 nm) and yellow (564 nm). Sensitivity below 350 nm is very low due to filtering by the UV-absorbing cornea. The set of photoreceptors represents the retinal substrate for putative trichromatic color vision.

UV-B-Induced CPD Photolyase Gene Expression is Regulated by UVR8-Dependent and -Independent Pathways in Arabidopsis.

Plants have evolved various mechanisms that protect against the harmful effects of UV-B radiation (280-315 nm) on growth and development. Cyclobutane pyrimidine dimer (CPD) photolyase, the repair enzyme for UV-B-induced CPDs, is essential for protecting cells from UV-B radiation. Expression of the CPD photolyase gene (PHR) is controlled by light with various wavelengths including UV-B, but the mechanisms of this regulation remain poorly understood. In this study, we investigated the regulation of PHR expression by light with various wavelengths, in particular low-fluence UV-B radiation (280 nm, 0.2 µmol m(-2) s(-1)), in Arabidopsis thaliana seedlings grown under light-dark cycles for 7 d and then adapted to the dark for 3 d. Low-fluence UV-B radiation induced CPDs but not reactive oxygen species. AtPHR expression was effectively induced by UV-B, UV-A (375 nm) and blue light. Expression induced by UV-A and blue light was predominantly regulated by the cryptochrome-dependent pathway, whereas phytochromes A and B played a minor but noticeable role. Expression induced by UV-B was predominantly regulated by the UVR8-dependent pathway. AtPHR expression was also mediated by a UVR8-independent pathway, which is correlated with CPD accumulation induced by UV-B radiation. These results indicate that Arabidopsis has evolved diverse mechanisms to regulate CPD photolyase expression by multiple photoreceptor signaling pathways, including UVR8-dependent and -independent pathways, as protection against harmful effects of UV-B radiation.

A Constitutively Active Allele of Phytochrome B Maintains Circadian Robustness in the Absence of Light.

The sensitivity of the circadian system to light allows entrainment of the clock, permitting coordination of plant metabolic function and flowering time across seasons. Light affects the circadian system via both photoreceptors, such as phytochromes and cryptochromes, and sugar production by photosynthesis. In the present study, we introduce a constitutively active version of phytochrome B-Y276H (YHB) into both wild-type and phytochrome null backgrounds of Arabidopsis (Arabidopsis thaliana) to distinguish the effects of photoreceptor signaling on clock function from those of photosynthesis. We find that the YHB mutation is sufficient to phenocopy red light input into the circadian mechanism and to sustain robust rhythms in steady-state mRNA levels even in plants grown without light or exogenous sugars. The pace of the clock is insensitive to light intensity in YHB plants, indicating that light input to the clock is constitutively activated by this allele. Mutation of YHB so that it is retained in the cytoplasm abrogates its effects on clock function, indicating that nuclear localization of phytochrome is necessary for its clock regulatory activity. We also demonstrate a role for phytochrome C as part of the red light sensing network that modulates phytochrome B signaling input into the circadian system. Our findings indicate that phytochrome signaling in the nucleus plays a critical role in sustaining robust clock function under red light, even in the absence of photosynthesis or exogenous sources of energy.

Cx36 expression in the AII-mediated rod pathway is activity dependent in the developing rabbit retina.

Gap junctions are composed of connexin 36 (Cx36) and play a critical role in the rod photoreceptor signaling pathways of the vertebrate retina. Despite the fact that their connection and modulation in various rod pathways have been extensively studied in adult animals, little is known about the contribution and regulation of gap junctions to the development of the AII amacrine cell (AC)-mediated rod pathway. Using immunohistochemistry and microinjection, this study demonstrates a steady increase in relative Cx36 protein expression in both plexiform layers of the rabbit retina at around the time of eye opening. However, immediately after eye opening, most Cx36 immunoreactive AII ACs show no gap junction coupling pattern to neighboring cells and it is not until the third postnatal week that AII cells begin to exhibit an adult-like tracer-coupling pattern. Moreover, studies using dark-rearing and AMPA receptor blockade during postnatal development both revealed that relative levels of Cx36 immunoreactivity in AII ACs were increased when neural activity was inhibited. Our findings suggest that Cx36 expression in the AII-mediated rod pathway is activity dependent in the developing rabbit retina.

Differentiating Biological Colours with Few and Many Sensors: Spectral Reconstruction with RGB and Hyperspectral Cameras.

BackgroundThe ability to discriminate between two similar or progressively dissimilar colours is important for many animals as it allows for accurately interpreting visual signals produced by key target stimuli or distractor information. Spectrophotometry objectively measures the spectral characteristics of these signals, but is often limited to point samples that could underestimate spectral variability within a single sample. Algorithms for RGB images and digital imaging devices with many more than three channels, hyperspectral cameras, have been recently developed to produce image spectrophotometers to recover reflectance spectra at individual pixel locations. We compare a linearised RGB and a hyperspectral camera in terms of their individual capacities to discriminate between colour targets of varying perceptual similarity for a human observer.Main Findings(1) The colour discrimination power of the RGB device is dependent on colour similarity between the samples whilst the hyperspectral device enables the reconstruction of a unique spectrum for each sampled pixel location independently from their chromatic appearance. (2) Uncertainty associated with spectral reconstruction from RGB responses results from the joint effect of metamerism and spectral variability within a single sample.Conclusion(1) RGB devices give a valuable insight into the limitations of colour discrimination with a low number of photoreceptors, as the principles involved in the interpretation of photoreceptor signals in trichromatic animals also apply to RGB camera responses. (2) The hyperspectral camera architecture provides means to explore other important aspects of colour vision like the perception of certain types of camouflage and colour constancy where multiple, narrow-band sensors increase resolution.

Imaging Ca<sup>2+</sup> Dynamics in Cone Photoreceptor Axon Terminals of the Mouse Retina

Retinal cone photoreceptors (cones) serve daylight vision and are the basis of color discrimination. They are subject to degeneration, often leading to blindness in many retinal diseases. Calcium (Ca2+), a key second messenger in photoreceptor signaling and metabolism, has been proposed to be indirectly linked with photoreceptor degeneration in various animal models. Systematically studying these aspects of cone physiology and pathophysiology has been hampered by the difficulties of electrically recording from these small cells, in particular in the mouse where the retina is dominated by rod photoreceptors. To circumvent this issue, we established a two-photon Ca2+ imaging protocol using a transgenic mouse line that expresses the genetically encoded Ca2+ biosensor TN-XL exclusively in cones and can be crossbred with mouse models for photoreceptor degeneration. The protocol described here involves preparing vertical sections (“slices”) of retinas from mice and optical imaging of light stimulus-evoked changes in cone Ca2+ level. The protocol also allows “in-slice measurement” of absolute Ca2+ concentrations; as the recordings can be followed by calibration. This protocol enables studies into functional cone properties and is expected to contribute to the understanding of cone Ca2+ signaling as well as the potential involvement of Ca2+ in photoreceptor death and retinal degeneration.

Imaging Ca2+ dynamics in cone photoreceptor axon terminals of the mouse retina.

Retinal cone photoreceptors (cones) serve daylight vision and are the basis of color discrimination. They are subject to degeneration, often leading to blindness in many retinal diseases. Calcium (Ca2+), a key second messenger in photoreceptor signaling and metabolism, has been proposed to be indirectly linked with photoreceptor degeneration in various animal models. Systematically studying these aspects of cone physiology and pathophysiology has been hampered by the difficulties of electrically recording from these small cells, in particular in the mouse where the retina is dominated by rod photoreceptors. To circumvent this issue, we established a two-photon Ca2+ imaging protocol using a transgenic mouse line that expresses the genetically encoded Ca2+ biosensor TN-XL exclusively in cones and can be crossbred with mouse models for photoreceptor degeneration. The protocol described here involves preparing vertical sections (“slices”) of retinas from mice and optical imaging of light stimulus-evoked changes in cone Ca2+ level. The protocol also allows “in-slice measurement” of absolute Ca2+ concentrations; as the recordings can be followed by calibration. This protocol enables studies into functional cone properties and is expected to contribute to the understanding of cone Ca2+ signaling as well as the potential involvement of Ca2+ in photoreceptor death and retinal degeneration.

Larry Cohen—50 ways to DYE your science

Larry Cohen—50 ways to DYE your science

Evening expression of arabidopsis GIGANTEA is controlled by combinatorial interactions among evolutionarily conserved regulatory motifs.

Diurnal patterns of gene transcription are often conferred by complex interactions between circadian clock control and acute responses to environmental cues. Arabidopsis thaliana GIGANTEA (GI) contributes to photoperiodic flowering, circadian clock control, and photoreceptor signaling, and its transcription is regulated by the circadian clock and light. We used phylogenetic shadowing to identify three evolutionarily constrained regions (conserved regulatory modules [CRMs]) within the GI promoter and show that CRM2 is sufficient to confer a similar transcriptional pattern as the full-length promoter. Dissection of CRM2 showed that one subfragment (CRM2-A) contributes light inducibility, while another (CRM2-B) exhibits a diurnal response. Mutational analysis showed that three ABA RESPONSE ELEMENT LIKE (ABREL) motifs in CRM2-A and three EVENING ELEMENTs (EEs) in CRM2-B are essential in combination to confer a high amplitude diurnal pattern of expression. Genome-wide analysis identified characteristic spacing patterns of EEs and 71 A. thaliana promoters containing three EEs. Among these promoters, that of FLAVIN BINDING KELCH REPEAT F-BOX1 was analyzed in detail and shown to harbor a CRM functionally related to GI CRM2. Thus, combinatorial interactions among EEs and ABRELs confer diurnal patterns of transcription via an evolutionarily conserved module present in GI and other evening-expressed genes.

Spectral and spatial selectivity of luminance vision in reef fish.

Luminance vision has high spatial resolution and is used for form vision and texture discrimination. In humans, birds and bees luminance channel is spectrally selective—it depends on the signals of the long-wavelength sensitive photoreceptors (bees) or on the sum of long- and middle-wavelength sensitive cones (humans), but not on the signal of the short-wavelength sensitive (blue) photoreceptors. The reasons of such selectivity are not fully understood. The aim of this study is to reveal the inputs of cone signals to high resolution luminance vision in reef fish. Sixteen freshly caught damselfish, Pomacentrus amboinensis, were trained to discriminate stimuli differing either in their color or in their fine patterns (stripes vs. cheques). Three colors (“bright green”, “dark green” and “blue”) were used to create two sets of color and two sets of pattern stimuli. The “bright green” and “dark green” were similar in their chromatic properties for fish, but differed in their lightness; the “dark green” differed from “blue” in the signal for the blue cone, but yielded similar signals in the long-wavelength and middle-wavelength cones. Fish easily learned to discriminate “bright green” from “dark green” and “dark green” from “blue” stimuli. Fish also could discriminate the fine patterns created from “dark green” and “bright green”. However, fish failed to discriminate fine patterns created from “blue” and “dark green” colors, i.e., the colors that provided contrast for the blue-sensitive photoreceptor, but not for the long-wavelength sensitive one. High resolution luminance vision in damselfish, Pomacentrus amboinensis, does not have input from the blue-sensitive cone, which may indicate that the spectral selectivity of luminance channel is a general feature of visual processing in both aquatic and terrestrial animals.

Multiple Redundant Medulla Projection Neurons Mediate Color Vision in Drosophila

The receptor mechanism for color vision has been extensively studied. In contrast, the circuit(s) that transform(s) photoreceptor signals into color percepts to guide behavior remain(s) poorly characterized. Using intersectional genetics to inactivate identified subsets of neurons, we have uncovered the first-order interneurons that are functionally required for hue discrimination in Drosophila. We developed a novel aversive operant conditioning assay for intensity-independent color discrimination (true color vision) in Drosophila. Single flying flies are magnetically tethered in an arena surrounded by blue and green LEDs (light-emitting diodes). The flies’ optomotor response is used to determine the blue-green isoluminant intensity. Flies are then conditioned to discriminate between equiluminant blue or green stimuli. Wild-type flies are successfully trained in this paradigm when conditioned to avoid either blue or green. Functional color entrainment requires the function of the narrow-spectrum photoreceptors R8 and/or R7, and is within a limited range, intensity independent, suggesting that it is mediated by a color vision system. The medulla projection neurons, Tm5a/b/c and Tm20, receive direct inputs from R7 or R8 photoreceptors and indirect input from the broad-spectrum photoreceptors R1–R6 via the lamina neuron L3. Genetically inactivating these four classes of medulla projection neurons abolished color learning. However, inactivation of subsets of these neurons is insufficient to block color learning, suggesting that true color vision is mediated by multiple redundant pathways. We hypothesize that flies represent color along multiple axes at the first synapse in the fly visual system. The apparent redundancy in learned color discrimination sharply contrasts with innate ultraviolet (UV) spectral preference, which is dominated by a single pathway from the amacrine neuron Dm8 to the Tm5c projection neurons.

ROS-GC interlocked Ca(2+)-sensor S100B protein signaling in cone photoreceptors: review.

Photoreceptor rod outer segment membrane guanylate cyclase (ROS-GC) is central to visual transduction; it generates cyclic GMP, the second messenger of the photon signal. Photoexcited rhodopsin initiates a biochemical cascade that leads to a drop in the intracellular level of cyclic GMP and closure of cyclic nucleotide gated ion channels. Recovery of the photoresponse requires resynthesis of cyclic GMP, typically by a pair of ROS-GCs, 1 and 2. In rods, ROS-GCs exist as complexes with guanylate cyclase activating proteins (GCAPs), which are Ca2+-sensing elements. There is a light-induced fall in intracellular Ca2+. As Ca2+ dissociates from GCAPs in the 20–200 nM range, ROS-GC activity rises to quicken the photoresponse recovery. GCAPs then progressively turn down ROS-GC activity as Ca2+ and cyclic GMP levels return to baseline. To date, GCAPs mediate the only known mechanism of ROS-GC regulation in the photoreceptors. However, in mammalian cone outer segments, cone synapses and ON bipolar cells, another Ca2+ sensor protein, S100B, complexes with ROS-GC1 and senses the Ca2+ signal with a K1/2 of 400 nM. Unlike GCAPs, S100B stimulates ROS-GC activity when Ca2+ is bound. Thus, the ROS-GC system in cones functions as a Ca2+ bimodal switch; with rising intracellular Ca2+, its activity is first turned down by GCAPs and then turned up by S100B. This presentation provides a historical perspective on the role of S100B in the photoreceptors, offers a pictorial model for the “bimodal” operation of the ROS-GC switch and projects future tasks that are needed to understand its operation. Some accounts of this review have been adopted from the original publications of these authors.

Accumulation of TIP2;2 Aquaporin during Dark Adaptation Is Partially PhyA Dependent in Roots of Arabidopsis Seedlings.

Light regulates the expression and function of aquaporins, which are involved in water and solute transport. In Arabidopsis thaliana, mRNA levels of one of the aquaporin genes, TIP2;2, increase during dark adaptation and decrease under far-red light illumination, but the effects of light at the protein level and on the mechanism of light regulation remain unknown. Numerous studies have described the light regulation of aquaporin genes, but none have identified the regulatory mechanisms behind this regulation via specific photoreceptor signaling. In this paper, we focus on the role of phytochrome A (phyA) signaling in the regulation of the TIP2;2 protein. We generated Arabidopsis transgenic plants expressing a TIP2;2-GFP fusion protein driven by its own promoter, and showed several differences in TIP2;2 behavior between wild type and the phyA mutant. Fluorescence of TIP2;2-GFP protein in the endodermis of roots in the wild-type seedlings increased during dark adaptation, but not in the phyA mutant. The amount of the TIP2;2-GFP protein in wild-type seedlings decreased rapidly under far-red light illumination, and a delay in reduction of TIP2;2-GFP was observed in the phyA mutant. Our results imply that phyA, cooperating with other photoreceptors, modulates the level of TIP2;2 in Arabidopsis roots.

Phototropism: Growing towards an Understanding of Plant Movement

Phototropism, or the differential cell elongation exhibited by a plant organ in response to directional blue light, provides the plant with a means to optimize photosynthetic light capture in the aerial portion and water and nutrient acquisition in the roots. Tremendous advances have been made in our understanding of the molecular, biochemical, and cellular bases of phototropism in recent years. Six photoreceptors and their associated signaling pathways have been linked to phototropic responses under various conditions. Primary detection of directional light occurs at the plasma membrane, whereas secondary modulatory photoreception occurs in the cytoplasm and nucleus. Intracellular responses to light cues are processed to regulate cell-to-cell movement of auxin to allow establishment of a trans-organ gradient of the hormone. Photosignaling also impinges on the transcriptional regulation response established as a result of changes in local auxin concentrations. Three additional phytohormone signaling pathways have also been shown to influence phototropic responsiveness, and these pathways are influenced by the photoreceptor signaling as well. Here, we will discuss this complex dance of intra- and intercellular responses that are regulated by these many systems to give rise to a rapid and robust adaptation response observed as organ bending.

Presynaptic [Ca2+] and GCAPs: aspects on the structure and function of photoreceptor ribbon synapses

Changes in intracellular calcium ions [Ca2+] play important roles in photoreceptor signaling. Consequently, intracellular [Ca2+] levels need to be tightly controlled. In the light-sensitive outer segments (OS) of photoreceptors, Ca2+ regulates the activity of retinal guanylate cyclases thus playing a central role in phototransduction and light-adaptation by restoring light-induced decreases in cGMP. In the synaptic terminals, changes of intracellular Ca2+ trigger various aspects of neurotransmission. Photoreceptors employ tonically active ribbon synapses that encode light-induced, graded changes of membrane potential into modulation of continuous synaptic vesicle exocytosis. The active zones of ribbon synapses contain large electron-dense structures, synaptic ribbons, that are associated with large numbers of synaptic vesicles. Synaptic coding at ribbon synapses differs from synaptic coding at conventional (phasic) synapses. Recent studies revealed new insights how synaptic ribbons are involved in this process. This review focuses on the regulation of [Ca2+] in presynaptic photoreceptor terminals and on the function of a particular Ca2+-regulated protein, the neuronal calcium sensor protein GCAP2 (guanylate cyclase-activating protein-2) in the photoreceptor ribbon synapse. GCAP2, an EF-hand-containing protein plays multiple roles in the OS and in the photoreceptor synapse. In the OS, GCAP2 works as a Ca2+-sensor within a Ca2+-regulated feedback loop that adjusts cGMP levels. In the photoreceptor synapse, GCAP2 binds to RIBEYE, a component of synaptic ribbons, and mediates Ca2+-dependent plasticity at that site. Possible mechanisms are discussed.

High-Resolution Imaging of Patients with Bietti Crystalline Dystrophy with CYP4V2 Mutation.

The purpose of this study was to determine the retinal morphology of eyes with Bietti crystalline dystrophy (BCD) associated with a CYP4V2 mutation using high-resolution imaging techniques. Three subjects with BCD underwent detailed ophthalmic examinations. High-resolution fundus images were obtained with an adaptive optics (AO) fundus camera. A common homozygous mutation was detected in the three patients. Funduscopic examination of the three patients revealed the presence of crystalline deposits in the retina, and all of the crystalline deposits were also detected in the infrared (IR) images. The crystals observed in the IR images were seen as bright reflective plaques located on the RPE layer in the SD-OCT images. The clusters of hyperreflective signals in the AO images corresponded to the crystals in the IR images. High-magnification AO images revealed that the clusters of hyperreflective signals consisted of circular spots that are similar to the signals of cone photoreceptors. Most of these circular spots were detected in healthy areas in the FAF images. There is a possibility that circular spots observed by AO are residual cone photoreceptors located over the crystals.