Oguchi Disease Research Articles

Visual Arrestin 1 Acts As a Modulator for N-Ethylmaleimide-Sensitive Factor in the Photoreceptor Synapse

In the G-protein-coupled receptor phototransduction cascade, visual Arrestin 1 (Arr1) binds to and deactivates phosphorylated light-activated opsins, a process that is critical for effective recovery and normal vision. In this report, we discovered a novel synaptic interaction between Arr1 and N-ethylmaleimide-sensitive factor (NSF) that is enhanced in a dark environment when mouse photoreceptors are depolarized and the rate of exocytosis is elevated. In the photoreceptor synapse, NSF functions to sustain a higher rate of exocytosis, in addition to the compensatory endocytosis to retrieve and to recycle vesicle membrane and synaptic proteins. Not only does Arr1 bind to the junction of NSF N-terminal and its first ATPase domains in an ATP-dependent manner in vitro, but Arr1 also enhances both NSF ATPase and NSF disassembly activities. In in vivo experiments in mouse retinas with the Arr1 gene knocked out, the expression levels of NSF and other synapse-enriched components, including vGLUT1 (vesicular glutamate transporter 1), EAAT5 (excitatory amino acid transporter 5), and VAMP2 (vesicle-associated membrane protein 2), are markedly reduced, which leads to a substantial decrease in the exocytosis rate with FM1-43. Thus, we propose that the Arr1 and NSF interaction is important for modulating normal synaptic function in mouse photoreceptors. This study demonstrates a vital alternative function for Arr1 in the photoreceptor synapse and provides key insights into the potential molecular mechanisms of inherited retinal diseases, such as Oguchi disease and Arr1-associated retinitis pigmentosa.

KMeyeDB: a graphical database of mutations in genes that cause eye diseases

KMeyeDB (http://mutview.dmb.med.keio.ac.jp/) is a database of human gene mutations that cause eye diseases. We have substantially enriched the amount of data in the database, which now contains information about the mutations of 167 human genes causing eye-related diseases including retinitis pigmentosa, cone-rod dystrophy, night blindness, Oguchi disease, Stargardt disease, macular degeneration, Leber congenital amaurosis, corneal dystrophy, cataract, glaucoma, retinoblastoma, Bardet-Biedl syndrome, and Usher syndrome. KMeyeDB is operated using the database software MutationView, which deals with various characters of mutations, gene structure, protein functional domains, and polymerase chain reaction (PCR) primers, as well as clinical data for each case. Users can access the database using an ordinary Internet browser with smooth user-interface, without user registration. The results are displayed on the graphical windows together with statistical calculations. All mutations and associated data have been collected from published articles. Careful data analysis with KMeyeDB revealed many interesting features regarding the mutations in 167 genes that cause 326 different types of eye diseases. Some genes are involved in multiple types of eye diseases, whereas several eye diseases are caused by different mutations in one gene.

Site-specific Phosphorylation of CXCR4 Is Dynamically Regulated by Multiple Kinases and Results in Differential Modulation of CXCR4 Signaling

The chemokine receptor CXCR4 is a widely expressed G protein-coupled receptor that has been implicated in a number of diseases including human immunodeficiency virus, cancer, and WHIM syndrome, with the latter two involving dysregulation of CXCR4 signaling. To better understand the role of phosphorylation in regulating CXCR4 signaling, tandem mass spectrometry and phospho-specific antibodies were used to identify sites of agonist-promoted phosphorylation. These studies demonstrated that Ser-321, Ser-324, Ser-325, Ser-330, Ser-339, and two sites between Ser-346 and Ser-352 were phosphorylated in HEK293 cells. We show that Ser-324/5 was rapidly phosphorylated by protein kinase C and G protein-coupled receptor kinase 6 (GRK6) upon CXCL12 treatment, whereas Ser-339 was specifically and rapidly phosphorylated by GRK6. Ser-330 was also phosphorylated by GRK6, albeit with slower kinetics. Similar results were observed in human astroglia cells, where endogenous CXCR4 was rapidly phosphorylated on Ser-324/5 by protein kinase C after CXCL12 treatment, whereas Ser-330 was slowly phosphorylated. Analysis of CXCR4 signaling in HEK293 cells revealed that calcium mobilization was primarily negatively regulated by GRK2, GRK6, and arrestin3, whereas GRK3, GRK6, and arrestin2 played a primary role in positively regulating ERK1/2 activation. In contrast, GRK2 appeared to play a negative role in ERK1/2 activation. Finally, we show that arrestin association with CXCR4 is primarily driven by the phosphorylation of far C-terminal residues on the receptor. These studies reveal that site-specific phosphorylation of CXCR4 is dynamically regulated by multiple kinases resulting in both positive and negative modulation of CXCR4 signaling.

Optical coherence tomographic evaluation of the outer retinal architecture in Oguchi disease

To report the changes in the optical coherence tomography (OCT) images of the outer retinal layers after prolonged dark adaptation in a patient with Oguchi disease. A 75-year-old woman showed the typical golden-yellow fundus reflex of Oguchi disease, and the coloration returned to normal after prolonged dark adaptation. Fourier domain OCT (FD-OCT) was performed on the patient's left eye before and after prolonged dark adaptation. Before dark adaptation, the FD-OCT images at the fovea had three identifiable reflection bands, namely, the external limiting membrane (ELM), the border between the photoreceptor inner and outer segments (IS/OS line), and the retinal pigment epithelium (RPE)/Bruch band. The paramacular area had only the ELM and RPE/Bruch bands. After 4 h of dark adaptation, the IS/OS line was also detected in the paramacular area. The absence of the IS/OS line in the extramacular regions in the partly dark adapted condition was most likely due to a defect in the rod photoreceptors of this area. The emergence of the IS/OS line after prolonged dark adaptation suggests that microarchitectural changes occur in the photoreceptors and that the changes may be correlated with the improvement of rod function.

Shortening of the rod outer segment in Oguchi disease

Dear Editor, Oguchi disease, characterized by stationary night blindness, is an inherited and non-progressive retinal disorder that affects the rods and causes impaired night vision [1]. Histologic findings have not been reported. We observed microstructural change of the retina in Oguchi disease using spectral domain optical coherence tomography (SD-OCT). A 31-year-old man had night blindness since childhood. His best-corrected visual acuity was 1.2 bilaterally. On ophthalmoscopic examination (Fig. 1), his fundus had a golden sheen reflex, except for the macular and perimacular areas. The macula had a normal red reflex, but the perimacular area was grayish bilaterally. A full-field ERG showed normal cone and flicker responses; the rod response was non-recordable. Multifocal ERG showed a normal response. The visual field was within normal limits on Goldmann perimetry. He was diagnosed with Oguchi disease. Oguchi disease has five subtypes depending on the location of the golden sheen reflex, i.e., the entire fundus, macula sparing, posterior fundus sparing, peripheral sparing, and far periphery sparing. The current case corresponds to the posterior fundus-sparing type. In a horizontal 6-mm scan across the fovea, the junction between photoreceptor inner and outer segment (IS/OS ) appeared normal in the macula within a 3-mm diameter; however, the distance between the IS/OS and retinal pigment epithelium (RPE) suddenly decreased, and the IS/ OS line was not identifiable in a 3-mm-wide perimacular ring, where the retina was attenuated because of decreased thickness of the outer nuclear layer (ONL). The IS/OS line emerged outside of the perimacular ring in the midperiphery, but the distance between the IS/OS and RPE was short, such that the two reflective lines fused into one broad reflective band in some areas. The midperipheral retinal thickness was normal. SD-OCT (Fig. 2) showed that the distance between the IS/OS line and RPE was short in the midperipheral fundus, which had a golden sheen. However, the IS/OS line appeared normal in the macula, where the fundus color was normal. The IS/OS line was not identifiable in the perimacular area, where the fundus was grayish, resembling an early change in retinitis pigmentosa. Since the IS/OS line indicates high reflectivity at the proximal portion of the photoreceptor outer segment, the decreased distance between the IS/OS and the RPE suggests shortening of the outer segment. OCT suggested that the lesion responsible for the golden sheen reflex appeared to be shortening of the rod outer segment. Full-field ERG showed a normal cone response and a non-recordable rod response. Since the cones were intact, the IS/OS appeared normal in the macula where the cones aggregate, and the fundus reflex was normal. It was noteworthy that the fundus reflex was grayish in the perimacular area where the IS/OS was not identifiable with attenuation of the ONL. The loss of the Graefes Arch Clin Exp Ophthalmol (2009) 247:1561–1563 DOI 10.1007/s00417-009-1114-6

Age‐related reduction in retinal deimination levels in the F344BN rat

Increased deimination and peptidyl arginine deiminase type 2 (PAD2) expression has been observed in age-related neurodegenerative diseases without discrimination between their aging and disease component. Here, we describe reduced levels of deimination commensurate with reduced protein, mRNA and activity of peptidylarginine deiminase type 2 in the retina, optic nerve and plasma of aged rats when compared to young rats. The decrease was significant in the ganglion cell layer, inner plexiform layer and inner nuclear layer. Because our observations suggest reduced deimination is a consequence of aging, we conclude that increased deimination must be a consequence of disease. Our findings are important to understand late-onset and progressive diseases such as glaucoma, pseudoexfoliation syndrome, age-related macular degeneration and Oguchi's disease.

A case of Oguchi's disease with diabetic retinopathy

A 50-year-old Iranian diabetic woman with night blindness was referred to our clinic. Complete ophthalmic examination including ophthalmoscopy after dark adaptation and paraclinic evaluations such as fluorescein angiography and electroretinography were performed. Retinal neovascularization and preretinal haemorrhages compatible with high-risk characteristic proliferative diabetic retinopathy were observed bilaterally. In addition, a golden-yellowish discoloration of posterior pole was noted in her both eyes. The diagnosis of Oguchi's disease was made when this discoloration disappeared after dark adaptation for 3 h. Electroretinograms also confirmed the diagnosis by showing a slow negative wave followed by a slow positive wave in the photopic condition and absent a- and b-waves in the scotopic state. We concluded that proliferative diabetic retinopathy might occur in a patient with Oguchi's disease. This report represents this association in an Iranian patient for the first time.

Novel Mutations in the GRK1 Gene in Japanese Patients With Oguchi Disease

To report novel mutations in the GRK1 gene in Japanese patients with Oguchi disease. Observational case report. Two unrelated Japanese patients with Oguchi disease were examined. After informed consent was obtained, the coding regions of SAG and GRK1 were analyzed by direct sequencing. Although no mutation was found in SAG, two novel homozygous mutations in GRK1, c.1079 del T and c.1408-1412 CCCCC to CCC, were identified. Both mutations are expected to generate null alleles of GRK1. The authors found two different novel mutations in Japanese patients. The results indicate that a considerable number of GRK1 mutations exist in the Japanese population.

Syndrome d’Oguchi ou cécité nocturne congénitale stationnaire : à propos d’un cas

Oguchi disease, originally described in Japanese people, is a rare form of stationary night blindness in patients with normal acuity. We report the case of an 8-year-old girl who presented with an abnormal terrified behavior in the dark. Thorough questioning revealed hemeralopia. Her clinical examination (visual acuity, Goldmann visual field, and color vision) were normal. The fundus examination showed golden-brown color, grayish, almost greenish yellow discoloration in the peripheral area with no osteoclast. This abnormality disappeared after prolonged dark adaptation. The electroretinogram showed a reduced b wave amplitude under scotopic conditions. Her parents were cousins. This diagnosis should be suggested when hemeralopia is associated with typical fundus aspect resolving after dark adaptation (so called Mizuo-Nakamura phenomenon). The long-term prognosis in these patients is good in the absence of clinical progression. This is a genetic autosomal recessive disease caused by mutations in the gene coding for arrestin located in 2q37.1.

A Novel Homozygous GRK1 Mutation (P391H) in 2 Siblings with Oguchi Disease with Markedly Reduced Cone Responses

The only mutations reported to date in Japanese patients with Oguchi disease, a rare form of stationary night blindness with autosomal recessive transmission, have been in the SAG (arrestin) gene. The objective of this study was to describe the ophthalmic features and a novel mutation in the GRK1 (rhodopsin kinase) gene in 2 Japanese patients with Oguchi disease. Molecular genetic and observational case study. A consanguineous family including 2 siblings with Oguchi disease (a 35-year-old man and a 31-year-old woman). Best-corrected visual acuity (BCVA), fundus examinations, Goldmann perimetry, color vision tests, and full-field electroretinograms (ERGs) were evaluated. Mutation screening of the SAG and GRK1 genes was performed with polymerase chain reaction amplification and direct sequencing. Mutations in the GRK1 gene, BCVA, color vision, fundus photographs, visual fields, and ERG findings. Molecular analysis revealed a novel homozygous missense mutation (p.P391H) in the GRK1 gene in both patients. Proline 391 is not only within the functionally important catalytic domain, but is also a phylogenetically conserved amino acid residue among GRK1 orthologs and homologs. No mutation was found in the SAG gene. The unaffected parents were heterozygous carriers of the mutation. Both patients had night blindness, 1.5 BCVA for each eye, normal color vision, and typical fundus appearance with golden-yellow discoloration. The visual fields were normal in the male sibling. The ERGs showed no rod B waves, reduced standard combined responses, and markedly reduced single-flash cone and 30-Hz flicker responses in both patients. A novel homozygous GRK1 mutation (p.P391H) was found in 2 Japanese siblings with Oguchi disease. Visual function in the 2 patients has not deteriorated with age, indicating that the disease is stationary. This is the first report of any patient with GRK1-associated Oguchi disease with markedly reduced cone responses.

Arrestin can act as a regulator of rhodopsin photochemistry

We report that visual arrestin can regulate retinal release and late photoproduct formation in rhodopsin. Our experiments, which employ a fluorescently labeled arrestin and rhodopsin solubilized in detergent/phospholipid micelles, indicate that arrestin can trap a population of retinal in the binding pocket with an absorbance characteristic of Meta II with the retinal Schiff-base intact. Furthermore, arrestin can convert Metarhodopsin III (formed either by thermal decay or blue-light irradiation) to a Meta II-like absorbing species. Together, our results suggest arrestin may be able to play a more complex role in the rod cell besides simply quenching transducin activity. This possibility may help explain why arrestin deficiency leads to problems like stationary night blindness (Oguchi disease) and retinal degeneration.

GRK et arrestines : la piste thérapeutique ?

Phosphorylation of the agonist-activated form of G-protein-coupled receptors (GPCRs) by a protein kinase from the G-protein-coupled receptor kinase (GRK) family initiates, with arrestin proteins, a negative feedback process known as desensitization. Because these receptors are involved in so many vital functions, it seems likely that disorders affecting GRK- or arrestin-mediated regulation of GPCRs would contribute to, if not engender, disease. Traditionally, it is believed that the desensitization process protects the cell against an overstimulation; however, in certain situations, this process is maladjusted and participes in disease progression. For example, in Oguchi disease, excessive rhodopsin stimulation due to a functional loss of GRK1 or arrestin 1 leads to light sensitization and stationary night blindness. Also, transgenic mice with vascular smooth muscle-targeted overexpression of GRK2 showed an elevated resting blood pressure, suggesting that increase in GRK2 level in humans is involved in hypertension associated with a decreased effect of beta-adrenergic receptor-mediated vasorelaxation. The restoration of normal GPCR function in modulating the desensitization process has been successfully demonstrated in animal models of heart failure, which indicates that targeting GRKs or arrestins may open a novel therapeutic strategy in human diseases with GPCR dysregulation. However, the few effective pharmacological compounds in this domain currently preclude human clinical tests.

Novel mutations in the arrestin gene and associated clinical features in Japanese patients with Oguchi's disease

Purpose Only 2 mutations in the arrestin gene have been previously reported to be associated with Oguchi's disease, a homozygous Asn309(1-bp del) mutation in Japanese families and a homozygous Arg193stop mutation in an Indian family. The aim of this article is to report 2 novel mutations in the arrestin gene in 2 Japanese patients with Oguchi's disease and to describe the clinical features with the mutations. Design Molecular genetic study and observational case report. Participants Two unrelated Japanese patients with Oguchi's disease associated with novel arrestin mutations. Methods Genomic DNA was extracted from leukocytes of the peripheral blood, and exons 2 through 16 of the arrestin gene were amplified by polymerase chain reaction and directly sequenced. A complete ophthalmologic examination was performed, including best-corrected visual acuity, slit-lamp and fundus examinations, fundus photography, and electroretinography (ERG). Main outcome measures Direct sequencing of the arrestin gene, evaluation of visual acuity, refraction, and ERG. Results Three arrestin gene mutations were identified in 2 patients. A compound heterozygous mutation, Arg175stop and Asn309(1-bp del), was identified in 1 patient with Oguchi's disease. The former mutation has not been reported, whereas the latter is known to be a frequent mutation in Oguchi's disease in Japanese families. In a second patient, another novel mutation was detected in the gene, a homozygous Arg292stop mutation. Both patients demonstrated characteristic features of Oguchi's disease, including night blindness, golden-yellow discoloration of the retina, absent rod ERG response, and “negative” type bright-flash ERG after 30 minutes of dark adaptation. Conclusions The existence of 2 novel mutations of the arrestin gene in 2 unrelated Japanese patients strongly supports the previous data that arrestin gene mutations are associated with Oguchi's disease. All of the mutations in the arrestin gene that have been identified in Oguchi's disease are null mutations, indicating that only critical gene defects in the arrestin gene are associated with Oguchi's disease.

Gene analysis and evaluation of the single founder effect in Japanese patients with Oguchi disease.

To analyze mutations of the arrestin/S-antigen (SAG) gene in nine newly identified Oguchi disease patients, and to examine whether the 926delA (formerly called 1147delA) mutation in the SAG gene is inherited from a single founder. DNA samples were assayed for mutations around nucleotide 926 of the SAG gene by direct sequencing, and analyzed for polymorphisms at codon 403 and IVS6-18 of the SAG gene by restriction analysis of polymerase chain reaction products. All nine newly identified patients were homozygous for the 926delA mutation and had the same haplotype at codon 403 and IVS6-18. These findings are identical to those of previous reports of four Japanese Oguchi disease patients. Mutation 926delA of the SAG gene is the main cause of Oguchi disease in Japanese. This mutation appears to have been inherited from a single founder.

Dark adaptation and the retinoid cycle of vision.

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

ERG rod a-wave in Oguchi disease

We analyzed the change in the ERG rod a-wave waveform during the course of dark adaptation in two patients with Oguchi disease. Two Japanese patients showed a homozygous arrestin 1147delA mutation. Scotopic flash ERGs were recorded after different periods of dark adaptation. ERG rod a-waves were obtained after subtraction of the cone ERG contribution. The rod a-waves were fitted with a model of the rod receptor signal. The parameters, Rm p3 ( maximum a-wave amplitude) and S ( sensitivity) were calculated. Longer periods in the dark produced larger rod a-wave but only to the first flash presented. The amplitude of the response to subsequent flashes was essentially independent of the period of dark adaptation. Rm p3 increased with advance of dark adaptation. However, S was nearly constant. Our results suggest that the cause of delayed dark adaptation is not to be sought in the activation of phototransduction process or the regeneration of rhodopsin per se but rather in the deactivation process of the phototransduction cascade.

Cone deactivation kinetics and GRK1/GRK7 expression in enhanced S cone syndrome caused by mutations in NR2E3.

To determine the relationship between cone deactivation kinetics in patients with the enhanced S cone syndrome (ESCS) caused by mutations in NR2E3 and the immunoreactivity to G-protein-coupled receptor kinase 1 (GRK1) and GRK7. Electroretinogram (ERG) photoresponses were used to investigate activation kinetics of cones with a model of cone phototransduction. Deactivation kinetics of cones after bright flashes was quantified with a paired-flash ERG paradigm. Immunocytochemistry was performed with antibodies against cone opsins and kinases GRK1 and GRK7 in postmortem normal and ESCS retinal tissue. Activation kinetics of long/middle-wavelength-sensitive (L/M) cone-mediated responses in patients with ESCS were similar to those of normal L/M cones. Activation kinetics of ESCS short-wavelength-sensitive (S) cones, when compared with normal L/M cone responses evoked by the same stimulus, were slower by an amount consistent with the expected differences in spectral sensitivities. After bright flashes chosen to evoke identical activation kinetics, ESCS S cones deactivated much more slowly than ESCS or normal L/M cones. Normal human retina revealed strongly labeled cone outer segments with anti-GRK1 and anti-GRK7. In an ESCS retina, outer segments positive for L/M opsin were strongly labeled with anti-GRK1, whereas outer segments positive for S opsin showed no detectable GRK1 reactivity. GRK7 labeling was absent in all photoreceptors of the ESCS retina. The cone-dominant human retina resulting from NR2E3 mutations affords greater understanding of the physiological roles of GRK1 and GRK7 in human cone photoreceptors. Normal deactivation kinetics in human L/M cones can occur without GRK7 when GRK1 is present in ESCS, but does not occur when GRK7 is present but GRK1 is deficient in Oguchi disease. Lack of both GRK1 and GRK7 in S cones of patients with ESCS results in a more pronounced abnormality in deactivation kinetics and suggests the existence of partial compensation by either GRK when the other is deficient.

Doença de Oguchi: relato de caso e revisão bibliográfica

Relatamos o caso de uma paciente com sintomas de cegueira noturna congenita estacionaria (CNCE) no qual constatamos alteracoes oftalmoscopicas peculiares da doenca de Oguchi, inedita, nos limites de nosso conhecimento, a consideracao da literatura medica brasileira publicada. Observamos e documentamos as alteracoes classicas desta doenca e do seu importante comemorativo, o tambem infrequente, fenomeno de Mizuo-Nakamura. O exame eletrorretinografico (ERG) tambem mostrou sinais tipicos. Acrescentamos, brevemente, revisao bibliografica da doenca.

Molecular genetics of Oguchi disease, fundus albipunctatus, and other forms of stationary night blindness: LVII Edward Jackson Memorial Lecture

PURPOSE: To compare the clinical findings of the various forms of stationary night blindness caused by mutations in identified genes encoding proteins of photoreceptors or the retinal pigment epithelium. METHODS: Review of the visual acuities, visual fields, fundi, dark-adaptation curves, and electroretinograms from patients with stationary night blindness caused by mutations in the genes RHO, GNAT1, PDE6B, RHOK, SAG, RDH5, and CACNA1F, respectively encoding rhodopsin, the α subunit of rod transducin, the β subunit of rod cGMP-phosphodiesterase, rhodopsin kinase, arrestin, 11- cis retinol dehydrogenase, and a retinal L-type calcium channel. RESULTS: In the evaluated forms of stationary night blindness, the time course of dark adaptation and the characteristics of the electroretinogram indicate that rod photoreceptors are present and that they function, although abnormally. In night blindness resulting from defects in rhodopsin, the α subunit of rod transducin, or the β subunit of rod cGMP phosphodiesterase, rod photoreceptors respond only to light intensities far brighter than normal, and the sensitivity of rods to light is similar to that of normal individuals who are not dark adapted. In fundus albipunctatus and in Oguchi disease, the rod photoreceptors can achieve normal sensitivity to dim light but only after 2 or more hours of dark adaptation, compared with approximately 0.5 hours for normal individuals. In each of these forms of stationary night blindness, the poor rod sensitivity and the time course of dark adaptation correlate with the known or presumed physiologic abnormalities caused by the identified gene defects. Patients with some forms of stationary night blindness, such as fundus albipunctatus and Oguchi disease, may develop degeneration of the retina leading to severe loss of vision in later life. CONCLUSIONS: The identification of the mutant genes causing forms of stationary night blindness refines the classification of these diseases and enhances our understanding of the underlying physiologic defects. Ophthalmologists must be aware that although these diseases are traditionally categorized as “stationary,” some of them lead to reduced visual acuity or constricted visual fields, especially in older patients. Efforts to develop therapies for these diseases should concentrate on these more severe forms.

Mizuo phenomenon observed by scanning laser ophthalmoscopy in a patient with Oguchi disease

PURPOSE: To elucidate the origin of the abnormal fundus reflex in Oguchi disease. METHODS: The ocular fundus of a 63-year-old woman who showed a homozygous arrestin 1147delA mutation was observed by scanning laser ophthalmoscopy with the use of an argon blue laser (wavelength, 488 nm), a helium-neon laser (633 nm), and an infrared laser (780 nm). RESULTS: Diffuse, fine, white particles, which do not exist in normal subjects, were clearly demonstrated only with the helium-neon laser. After 4-hour dark adaptation, the abnormal particles disappeared, but then they reappeared gradually during 30 minutes of light adaptation, in accordance with the golden metallic reflex. CONCLUSION: The white particles found by helium-neon laser could be the origin of the abnormal fundus reflex in Oguchi disease.