Randomized trial of polychromatic blue-enriched light for circadian phase shifting, melatonin suppression, and alerting responses.

Wavelength comparisons have indicated that circadian phase-shifting and enhancement of subjective and EEG-correlates of alertness have a higher sensitivity to short wavelength visible light. The aim of the current study was to test whether polychromatic light enriched in the blue portion of the spectrum (17,000 K) has increased efficacy for melatonin suppression, circadian phase-shifting, and alertness as compared to an equal photon density exposure to a standard white polychromatic light (4000 K). Twenty healthy participants were studied in a time-free environment for 7 days. The protocol included two baseline days followed by a 26-h constant routine (CR1) to assess initial circadian phase. Following CR1, participants were exposed to a full-field fluorescent light (1 × 1014 photons/cm2/s, 4000 K or 17,000 K, n = 10/condition) for 6.5 h during the biological night. Following an 8 h recovery sleep, a second 30-h CR was performed. Melatonin suppression was assessed from the difference during the light exposure and the corresponding clock time 24 h earlier during CR1. Phase-shifts were calculated from the clock time difference in dim light melatonin onset time (DLMO) between CR1 and CR2. Blue-enriched light caused significantly greater suppression of melatonin than standard light ((mean ±â€¯SD) 70.9 ±â€¯19.6% and 42.8 ±â€¯29.1%, respectively, p < 0.05). There was no significant difference in the magnitude of phase delay shifts. Blue-enriched light significantly improved subjective alertness (p < 0.05) but no differences were found for objective alertness. These data contribute to the optimization of the short wavelength-enriched spectra and intensities needed for circadian, neuroendocrine and neurobehavioral regulation.

Comparison of effectiveness and safety between conbercept and ranibizumab for treatment of neovascular age-related macular degeneration. A retrospective case-controlled non-inferiority multiple center study.

PurposeTo compare the efficacy and safety of conbercept and ranibizumab when administered according to a treat-and-extend (TREX) protocol for the treatment of neovascular age-related macular degeneration (AMD) in China.Patients and methodsBetween May 2014 and May 2015, 180 patients were treated in a 1 : 1 ratio using conbercept or ranibizumab from four hospitals. Patients received either conbercept 0.5 mg or ranibizumab 0.5 mg intravitreal injections. Follow-up time was 1 year and treated based on a TREX approach. Main outcomes and measures include best-corrected visual acuity (BCVA), using Early Treatment Diabetic Retinopathy Study (ETDRS); number of injections; central retinal thickness (CRT); and leakage of choroidal neovascularization before and after the treatment was analyzed by fluorescein fundus angiography and indocyanine green angiography.ResultsThe 1-year visit was completed by 168 (93.3%) of patients. Mean BCVA was equivalent between two cohorts, and were improved by 12.7±7.770 and 12.3±7.269 letters in the conbercept and ranibizumab cohorts, respectively (P=0.624). There was no significant difference in measured CRT, with a mean decrease of 191.5 µm for conbercept and 187.8 µm for ranibizumab (P=0.773). There was a statistically significant difference (P=0.001) between the drugs regarding the number of treatments: 7.4 for conbercept and 8.7 for ranibizumab. The difference in the distribution of injection intervals was statistically significant between two groups (P=0.011). During the study, there were no cases of endophthalmitis or intraocular inflammation.ConclusionBoth drugs had equivalent effects in visual and anatomic gains at 1 year when administered. In the conbercept group, longer treatment intervals were achieved with more patients.

Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome.

Atypical hemolytic and uremic syndrome (aHUS) is a severe disease strongly associated with genetic abnormalities in the complement alternative pathway. In renal posttransplantation, few data are available on recurrence risk and graft outcome according to genetic background in aHUS patients. The aim of this study was to identify risk factors for recurrence and transplant outcome and, in particular, the role of complement gene abnormalities. We retrospectively studied 57 aHUS patients who had received 71 renal transplants. A mutation in complement gene was identified in 39 (68%), in factor H (CFH), factor I (CFI), membrane cofactor-protein (MCP), C3 and factor B (CFB). At 5 years, death-censored graft survival was 51%. Disease recurrence was associated with graft loss (p = 0.001). Mutations in complement genes were associated with higher risk of recurrence (p = 0.009). Patients with CFH or gain of function (C3, CFB) mutations had a highest risk of recurrence. M-TOR inhibitor was associated with significant risk of recurrence (p = 0.043) but not calcineurin inhibitor immunosuppressive treatment (p = 0.29). Preemptive plasmatherapy was associated with a trend to decrease recurrence (p = 0.07). Our study highlights that characterization of complement genetic abnormalities predicts the risk of recurrence-related graft loss and paves the way for future genetically based individualized prophylactic therapeutic strategies.

One year follow up in ischemic brain injury and the role of Alzheimer factors.

Ongoing interest in brain ischemia research has provided data showing that ischemia may be involved in the pathogenesis of Alzheimer disease. Brain ischemia in the rat produces a stereotyped pattern of selective neuronal degeneration, which mimics early Alzheimer disease pathology. The objective of this study was to further develop and characterize cardiac arrest model in rats, which provides practical way to analyze Alzheimer-type neurodegeneration. Rats were made ischemic by cardiac arrest. Blood-brain barrier (BBB) insufficiency, accumulation of different parts of amyloid precursor protein (APP) and platelets inside and outside BBB vessels were investigated in ischemic brain up to 1-year survival. Ischemic brain tissue demonstrated haphazard BBB changes. Toxic fragments of APP deposits were associated with the BBB vessels. Moreover our study revealed platelet aggregates in- and outside BBB vessels. Toxic parts of APP and platelet aggregates correlated very well with BBB permeability. Progressive injury of the ischemic brain parenchyma may be caused not only by a degeneration of neurons destroyed during ischemia but also by chronic damage in BBB. Chronic ischemic BBB insufficiency with accumulation of toxic components of APP in the brain tissue perivascular space, may gradually over a lifetime, progress to brain atrophy and to full blown Alzheimer-type pathology.

[Progressive multifocal leukoencephalopathy in a non-AIDS patient: high efficiency of combined cytarabine and cidofovir]. / Leucoencéphalite multifocale progressive en dehors du sida: efficacité de l'association cytarabine-cidofovir.

INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the central nervous system, occurring in immunocompromised patients. Treatment, not codified to date, is more often inefficient with a rapid and fatal deterioration. CASE RECORD: A 48-year-old woman, treated with immunosuppressant agents for systemic lupus, presented with PML mimicking neurolupus flare. A complete remission was obtained with cytarabine and cidofovir. CONCLUSION: Combined cytarabine and cidofovir appears a promising therapeutic option in PML associated with autoimmune systemic disorders.

Relationships between characteristics of interfacial water and human bone tissues.

Water bound in human bone tissues healthy (sample S1) and affected by osteoporosis (sample S2) was investigated by using 1H NMR spectroscopy with layer-by-layer freezing-out of bulk and interfacial waters at T< 273 K. The 1H NMR spectra of the bound water include two signals which can be assigned to strongly associated typical water (chemical shift of the proton resonance at delta(H) approximately 5 ppm) and weakly associated water at delta(H) approximately 1.4 ppm. Approximately, half of the bound water is in the weakly associated state in S1. A fraction of similar water in S2 is smaller because of the structural difference of the studied samples. The pore size distribution of S2 (in aqueous medium) calculated using the cryoporometry method is characterized by much larger intensity of mesopores and macropores in comparison with that of S1. The total porosity and the surface area of the biostructures (accessible for water molecules and estimated on the basis of the cryoporometry data using a model of cylindrical pores) are larger for S2. Weakly polar chloroform-d has a significant influence on the organization of water in a spongy component of bone tissue. This effect depends on the porosity of the bone matrix and the amounts of CDCl3.

Weakly and strongly associated nonfreezable water bound in bones.

Water bound in bone of rat tail vertebrae was investigated by 1H NMR spectroscopy at 210-300 K and by the thermally stimulated depolarization current (TSDC) method at 190-265 K. The 1H NMR spectra of water clusters were calculated by the GIAO method with the B3LYP/6-31G(d,p) basis set, and the solvent effects were analyzed by the HF/SM5.45/6-31G(d) method. The 1H NMR spectra of water in bone tissue include two signals that can be assigned to typical water (chemical shift of proton resonance deltaH=4-5 ppm) and unusual water (deltaH=1.2-1.7 ppm). According to the quantum chemical calculations, the latter can be attributed to water molecules without the hydrogen bonds through the hydrogen atoms, e.g., interacting with hydrophobic environment. An increase in the amount of water in bone leads to an increase in the amount of typical water, which is characterized by higher associativity (i.e., a larger average number of hydrogen bonds per molecule) and fills larger pores, cavities and pockets in bone tissue.

Necrotizing fasciitis during de novo minimal change nephrotic syndrome in a kidney transplant recipient.

Skin infections and particularly necrotizing fasciitis (NF) represent a rare but serious complication after transplantation. Optimal management depends on prompt diagnosis with identification of the causative organisms to allow appropriate antibiotic therapy in association with surgical debridement. We report a case of a methicillin-resistant Staphylococcus aureus (MRSA) NF as the single pathogen in a renal transplant recipient, during the course of a de novo minimal-change nephrotic syndrome, treated with high-dose steroids. Antibiotic therapy together with surgical debridement and discontinuation of immunosuppressive treatment led to a complete recovery, despite persistence of the nephrotic syndrome. The development of de novo minimal-change nephrotic syndrome after renal allograft transplantation should alert physicians to the possibility of MRSA NF during an increase in the immunosuppressive regimen.

Transitional fractures of the distal tibia.

INTRODUCTION: The purpose of the study was to determine the outcome after treatment of transitional fractures of the distal tibia, including growth disturbances, osteoarthritis, and/or restriction of the ability to take part in sports. PATIENTS AND METHODS: In a retrospective multicentre study of 72 patients, 50 were evaluated by clinical and 46 by radiographic examination, an average of 7.4 years (standard deviation 5.9) after treatment. Of these 50 patients, initially 20 were treated non-operatively and 30 were treated operatively. The mechanism was mainly supination trauma. RESULTS: There were four revision operations, including two for fracture displacement after earlier non-operative treatment. No patients reported impairment of sports activities. In no case was the range of movement in the upper ankle joint decreased by >10 degrees . Radiographic examination revealed small osteophytes in one case and narrowing of the joint space in two; there was no axial deviation or clinical problems in any of these cases. There were no significant differences between the group treated non-operatively and the group that underwent surgery. The intermediate- to long-term outcome presented was good or very good in both the surgically and conservatively treated patients. Only two of the initially nondisplaced fractures later became displaced. This finding emphasises that operative treatment is not indicated for all nondisplaced fractures. Axial deviations may not occur, because of the little growth potential of the partially closed physis.

Saturable absorbers incorporating carbon nanotubes directly synthesized onto substrates and fibers and their application to mode-locked fiber lasers.

We present novel carbon-nanotube-based saturable absorbers. Using the low-temperature alcohol catalytic chemical-vapor deposition method, high-quality single-walled carbon nanotubes (SWNTs) were directly synthesized on quartz substrates and fiber ends. We successfully applied the SWNTs to mode lock a fiber laser producing subpicosecond pulses at a 50-MHz repetition rate.

[Predicting growth patterns after supracondylar fracture of the humerus in childhood]. / Wie lässt sich die Wachstumsprognose nach kindlicher suprakondylärer Humerusfraktur erfassen?

Supracondylar fracture of the humerus is the most frequently investigated fracture in children. However, systematic studies about postoperative growth patterns cannot be found in the literature. In this retrospective study, the authors attempt to delineate the configuration of supracondylar fractures which allow spontaneous correction of a malalignment or cause post-traumatic growth disturbances. The study included 256 children with supracondylar fracture of the humerus: 184 of them (71.9%) were available for longterm follow-up. The plain films of these children were reviewed and the Baumann and shaft-capitulum angles recorded. Spontaneous correction of a primarily displaced fracture was found in 13.0% ( n=21) of all fractures in the sagittal plane. Spontaneous correction in the frontal plane could not be shown. Growth disturbance was discovered in 10.5% ( n=16) in the frontal plane. No growth disturbance was demonstrated in the sagittal plane. The relatively small number of growth disturbances can be attributed to the low growth potential of the distal physeal plate of the humerus. Growth disturbances with secondary rotational errors were not observed in this study. Spontaneous corrections of alignment in the sagittal plane are only possible under a certain age. Spontaneous correction in the frontal plane, however, is inadequately assessed with this study. The design of a prospective study was formulated to assess how to improve the therapeutic management of supracondylar fractures and to answer additional open questions. Follow-up radiographs and standardized clinical evaluations have to be performed at the time of first free range of movement and 2 years after the trauma. This study will investigate whether therapeutic progress at follow-up is better evaluated with radiological or clinical means.

Persistent expression of cyclin D1 disrupts normal photoreceptor differentiation and retina development.

The differentiation of neuronal cells in the developing mammalian retina is closely coupled to cell cycle arrest and proceeds in a highly organized manner. Cyclin D1, which regulates cell proliferation in many cells, also drives the proliferation of photoreceptor progenitors. In the mouse retina, cyclin D1 protein normally decreases as photoreceptors mature. To study the importance of the down-regulation of cyclin D1 during photoreceptor development, we generated a transgenic mouse in which cyclin D1 was persistently expressed in developing photoreceptor cells. We observed numerous abnormalities in both photoreceptors and other nonphotoreceptor cells in the retina of these transgenic mice. In particular, we observed delayed opsin expression in developing photoreceptors and alterations in their number and morphology in the mature retina. These alterations were accompanied by disorganization of the inner nuclear and plexiform layers. The expression of cyclin D1 caused excess photoreceptor cell proliferation and apoptosis. Loss of the p53 tumor suppressor gene decreased cyclin D1-induced apoptosis and led to microscopic hyperplasia in the retina. These findings are distinct from other mouse models in which the retinoblastoma gene pathway is disrupted and suggest that the IRBP-cyclin D1 mouse model may recapitulate an early step in the development of retinoblastoma.

Investigating the mechanisms of retinal degenerations with antisense oligonucleotides.

Utilizing antisense oligonucleotides coupled with an intact Xenopus eye rudiment model, we have effectively demonstrated that we are able to downregulate the expression of a photoreceptor-specific protein, rds/peripherin, and generate a loss-of-function model upon which to further study the function of the rds/peripherin gene. The ultrastructure and protein expression patterns very closely resemble those previously documented in both the rds mouse and in human autosomal dominant retinitis pigmentosa due to peripherin/RDS mutations. An identical strategy can be applied to any gene correlated with a degenerative retinal phenotype. As the entire array of genes is revealed through the various genome projects, including human and mouse, it is becoming increasingly critical to evaluate and determine the function of the corresponding gene products. Discovering which gene is responsible for a particular clinical phenotype is only the first of many steps in the development of a treatment or cure for that particular disease. Using our in vitro model, in which the retina is readily accessible to the antisense oligonucleotide yet the normal three-dimensional ultrastructure of the retina is maintained, we can evaluate the function of virtually any gene as the sequence becomes available. A thorough understanding of the function of individual genes will provide insights on the role of gene product in retinal health and pathophysiology. This experimental approach will also allow for specific therapeutic interventions to be evaluated so that targeted treatments can be designed for individuals with specific genetic mutations.

The concentrations of osteocalcin and degradation products of type I collagen in pregnant women with pre-eclampsia.

OBJECTIVES: To investigate the concentrations of osteocalcin and collagen type I C-terminal telopeptides in pregnant women with pre-eclampsia. STUDY DESIGN: 26 patients with severe pre-eclampsia and 24 healthy pregnant women were included in the study. Serum concentrations of osteocalcin and C-telopeptides--degradation products of type I collagen were determined using the ELISA method. Statistical analysis was performed using Mann-Whitney U-test. RESULTS: In pre-eclamptic patients, the concentrations of osteocalcin and degradation products of collagen type I were significantly higher (P<0.005) when compared to healthy pregnant women. CONCLUSION: These results could suggest that there are alterations in bone metabolism in pregnant women with pre-eclampsia.

Pigment epithelium-derived factor supports normal Müller cell development and glutamine synthetase expression after removal of the retinal pigment epithelium.

In conditions in which the retinal pigment epithelium (RPE) is dystrophic, carries a genetic mutation, or is removed physically, Müller cells undergo degenerative changes that contribute to the retinal pathology. We previously demonstrated that pigment epithelium-derived factor (PEDF), a glycoprotein secreted by the RPE cells with neuroprotective and differentiation properties, protects against photoreceptor degeneration induced by RPE removal. The purpose of the present study was to analyze the putative gliosupportive activity of PEDF on Müller cells of RPE-deprived retinas and assess whether protection of Müller cells was correlated with improved photoreceptor outer segment assembly. Eyes were dissected from Xenopus laevis tadpoles, and the RPE was removed before culturing in medium containing purified PEDF, PEDF plus anti-PEDF, or medium alone. Control eyes matured with an adherent RPE or in medium containing PEDF plus nonimmune serum. Müller cell ultrastructure was examined. Glial fibrillary acidic protein (GFAP) and glutamine synthetase were localized immunocytochemically, and the corresponding protein levels were quantified. In control retinas, Müller cells were structurally intact and formed adherens junctions with neighboring photoreceptors. In addition, they did not express GFAP, whereas glutamine synthetase expression was high. RPE removal dramatically altered the ultrastructure and biosynthetic activity of Müller cells; Müller cells failed to form adherens junctions with photoreceptors and glutamine synthetase expression was suppressed. PEDF prevented the degenerative glial response; Müller cells were ultrastructurally normal and formed junctional complexes with photoreceptors. PEDF also preserved the expression of glutamine synthetase at near-normal levels. The morphogenetic effects of PEDF were blocked by the anti-PEDF antibody. Our study documents the glioprotective effects of PEDF and suggests that maintenance of the proper Müller cell ultrastructure and expression of glutamine synthetase may be necessary to support the proper assembly of photoreceptor outer segments.

Reliability assessment of a rod photoreceptor outer segment grading system.

The purpose of this study was to assess the reliability of a rod photoreceptor outer segment (PR-OS) grading system based on the analysis of 1 microm thick retinal sections obtained from Xenopus laevis whole-eye organ cultures. Digitally captured images, representative of the entire spectrum of rod PR-OS organization levels, were selected and coded numerically. A total of 102 individual rod PR-OS profiles were graded according to a six-step classification scheme based on the percentage of rod PR-OS membrane organization. Unweighted (exact agreement) and weighted kappa (kappa) coefficients (for use with ordered categorical rating scales) were calculated. Differences between kappa coefficients were tested for by chi-square analysis. To investigate the intra- and inter-rater variability and the possible presence of an interaction of the measurements with time, a repeated-measures analysis of variance was performed. The overall unweighted and weighted intra-rater kappa coefficients were 0.78 and 0.92, respectively. The overall unweighted and weighted inter-rater kappa coefficients were 0.73 and 0.90, respectively. There was no significant difference between raters or between first and second reading, nor was interaction between raters and time of rating documented. Individual kappa coefficients were equivalent both between raters and between sessions. Intra- and inter-rater agreement was within one step in 100% of cases. The estimated values of the kappa coefficients are consistent with a good to excellent degree of reliability and reproducibility of this rod PR-OS grading system. This system will be useful in the assessment of rod PR-OS morphology in studies of photoreceptor physiology and pathology.

Lactose supports Muller cell protein expression patterns in the absence of the retinal pigment epithelium.

PURPOSE: We have previously shown that lactose, but not mannose, promotes the assembly of nascent photoreceptor outer segments in the absence of the retinal pigment epithelium (RPE). The purpose of the present study was to determine if, in addition to the improved outer segment assembly observed in the presence of lactose, biosynthetic changes in Muller cells could also be detected. METHODS: The RPE was removed from intact isolated Xenopus embryonic eyes that were allowed to complete differentiation in Niu-Twitty medium, Niu-Twitty with mannose, or Niu-Twitty with lactose. Control retinas matured in vitro with an adherent RPE. Retinal morphology was evaluated for organized folding of outer segment membranes and cell loss. In addition, the expression of three Muller cell proteins, glial fibrillary acidic protein (GFAP), cellular retinaldehyde-binding protein (CRALBP), and glutamine synthetase, was examined. RESULTS: In control retinas, GFAP is undetectable, CRALBP heavily immunolabels Muller cells, and radial patterns of glutamine synthetase immunoreactivity are present. In the absence of the RPE, Muller cells upregulate GFAP expression, CRALBP labeling is present at a slightly reduced level, and glutamine synthetase immunolabeling is negligible. Neither mannose nor lactose modify significantly the expression of CRALBP. Similarly, both compounds completely prevent the upregulation of GFAP. However, normal glutamine synthetase expression was observed only in the presence of lactose, but not in the presence of mannose. Statistical analyses of slot blot-based protein quantification confirmed our immunochemical results. CONCLUSIONS: In RPE-deprived retinas supplemented with lactose, Muller cells were morphologically normal. The proper photoreceptor outer segment morphogenesis observed under these conditions was uniquely associated with normal levels of glutamine synthetase expression. The exact significance of this finding with respect to photoreceptor outer segment morphogenesis is unknown. We suggest that glutamine synthetase may be a marker of Muller cell metabolic or structural integrity that may reflect the enhanced ability of these cells, in the presence of lactose, to support photoreceptor outer segment morphogenesis.

Pigment epithelium-derived factor supports normal development of photoreceptor neurons and opsin expression after retinal pigment epithelium removal.

Dysfunction of the retinal pigment epithelium (RPE), its loss, or separation from the underlying neural retina results in severe photoreceptor degeneration. Pigment epithelium-derived factor (PEDF) is a glycoprotein with reported neuroprotective and differentiation properties that is secreted in abundance by RPE cells. The "pooling" of PEDF within the interphotoreceptor matrix places this molecule in a prime physical location to affect the underlying neural retina. The purpose of this study was to analyze the morphogenetic activity of PEDF in a model of photoreceptor dysmorphogenesis induced by removal of the RPE. Eyes were dissected from embryonic Xenopus laevis, and the RPE was removed before culturing in medium containing PEDF, PEDF plus anti-PEDF antibodies, or medium alone. Control retinas were maintained with an adherent RPE. Light and electron microscopic analysis was used to examine retinal ultrastructure. Opsin was localized immunocytochemically and quantified as an index of outer segment membranous material and photoreceptor protein expression. Removal of the RPE resulted in an aberrant assembly of photoreceptor outer segments, loss of fine subcellular ultrastructure in photoreceptors, and a reduction in opsin protein levels when compared with control retinas. The addition of PEDF prevented the dysmorphic photoreceptor changes induced by RPE removal. In particular, photoreceptor ultrastructure, outer segment membrane assembly, and steady-state levels of opsin were equivalent to control conditions. Anti-PEDF antibodies completely blocked the morphogenetic activity of PEDF. These results indicate that PEDF is able to mimic the supportive role of the RPE on photoreceptors during the final stages of retinal morphogenesis.

Targeted disruption of Müller cell metabolism induces photoreceptor dysmorphogenesis.

Within the retina, the Müller cells and photoreceptors are in close physical proximity and are metabolically coupled. It is unknown, however, whether Müller cells affect photoreceptor differentiation and outer segment membrane assembly. The objective of this study was to determine whether targeted disruption of Müller cell metabolism would induce photoreceptor dysmorphogenesis. Intact isolated Xenopus laevis embryonic eyes were cultured in medium with or without Müller cell-specific inhibitors (i.e., alpha-aminoadipic acid and fluorocitrate). To assess Müller cell injury, the gross retinal morphology was examined along with immunocytochemical assessment of Müller cell-specific protein expression patterns. The steady-state levels of opsin were quantified to determine whether the Müller cell inhibitors negatively affected photoreceptor protein synthesis. Müller and photoreceptor cell ultrastructure was scrutinized and the organization of the outer segment membranes was graded. In control retinas, there was no swelling of Müller cell cytoplasm. Glial fibrillary acidic protein (GFAP) was undetectable, whereas glutamine synthetase was abundant. The steady-state level of opsin was high and photoreceptors elaborated properly folded outer segments. Exposure to both Müller cell-specific inhibitors induced swelling of Müller cell endfeet, cytoplasmic paling and alterations of Müller cell-specific protein expression patterns. The steady-state level of opsin in retinas exposed to alpha-aminoadipic acid was unchanged compared with control eyes, whereas, in eyes exposed to fluorocitrate, opsin levels were slightly reduced. The most significant finding was that targeted disruption of Müller cell metabolism adversely affected photoreceptor outer segment membrane assembly, causing dysmorphogenesis of nascent outer segments. These results suggest that the termination signal(s) necessary for proper outer segment folding were disrupted by targeted inhibition of Müller cells and support the hypothesis that Müller cells interact with photoreceptors through mechanisms that may regulate, at least in part, the assembly of photoreceptor outer segment membranes.