TRIPP Is a Plant-Specific Component of the Arabidopsis TRAPPII Membrane Trafficking Complex with Important Roles in Plant Development.

How the membrane trafficking system spatially organizes intracellular activities and intercellular signaling networks in plants is not well understood. Transport Protein Particle (TRAPP) complexes play key roles in the selective delivery of membrane vesicles to various subcellular compartments in yeast and animals but remain to be fully characterized in plants. Here, we investigated TRAPP complexes in Arabidopsis (Arabidopsis thaliana) using immunoprecipitation followed by quantitative mass spectrometry analysis of AtTRS33, a conserved core component of all TRAPP complexes. We identified 14 AtTRS33-interacting proteins, including homologs of all 13 TRAPP components in mammals and a protein that has homologs only in multicellular photosynthetic organisms and is thus named TRAPP-Interacting Plant Protein (TRIPP). TRIPP specifically associates with the TRAPPII complex through binary interactions with two TRAPPII-specific subunits. TRIPP colocalized with a subset of TRS33 compartments and trans-Golgi network markers in a TRS33-dependent manner. Loss-of-function tripp mutants exhibited dwarfism, sterility, partial photomorphogenesis in the dark, reduced polarity of the auxin transporter PIN2, incomplete cross wall formation, and altered localization of a TRAPPII-specific component. Therefore, TRIPP is a plant-specific component of the TRAPPII complex with important functions in trafficking, plant growth, and development.

Regularized quadratic cost-function for integrating wave-front gradient fields.

From the Bayesian regularization theory we derive a quadratic cost-function for integrating wave-front gradient fields. In the proposed cost-function, the term of conditional distribution uses a central-differences model to make the estimated function well consistent with the observed gradient field. As will be shown, the results obtained with the central-differences model are superior to the results obtained with the backward-differences model, commonly used in other integration techniques. As a regularization term we use an isotropic first-order differences Markov Random-Field model, which acts as a low-pass filter reducing the errors caused by the noise. We present simulated and real experiments of the proposal applied in the Foucault test, obtaining good results.

Foucault test: a quantitative evaluation method.

Reliable and accurate testing methods are essential to guiding the polishing process during the figuring of optical telescope mirrors. With the natural advancement of technology, the procedures and instruments used to carry out this delicate task have consistently increased in sensitivity, but also in complexity and cost. Fortunately, throughout history, the Foucault knife-edge test has shown the potential to measure transverse aberrations in the order of the wavelength, mainly when described in terms of physical theory, which allows a quantitative interpretation of its characteristic shadowmaps. Our previous publication on this topic derived a closed mathematical formulation that directly relates the knife-edge position with the observed irradiance pattern. The present work addresses the quite unexplored problem of the wavefront's gradient estimation from experimental captures of the test, which is achieved by means of an optimization algorithm featuring a proposed ad hoc cost function. The partial derivatives thereby calculated are then integrated by means of a Fourier-based algorithm to retrieve the mirror's actual surface profile. To date and to the best of our knowledge, this is the very first time that a complete mathematical-grounded treatment of this optical phenomenon is presented, complemented by an image-processing algorithm which allows a quantitative calculation of the corresponding slope at any given point of the mirror's surface, so that it becomes possible to accurately estimate the aberrations present in the analyzed concave device just through its associated foucaultgrams.

Foucault test: shadowgram modeling from the physical theory for quantitative evaluations.

The physical theory of the Foucault test has been investigated to represent the complex amplitude and irradiance of the shadowgram in terms of the wavefront error; however, most of the studies have limited the treatment for the particular case of nearly diffraction-limited optical devices (i.e., aberrations smaller than the wavelength). In this paper we discard this restriction, and in order to show a more precise interpretation from the physical theory we derive expressions for the complex amplitude and the irradiance over an optical device with larger aberrations. To the best of our knowledge, it is the first time an expression is obtained in closed form. As will be seen, the result of this derivation is obtained using some properties of the Hilbert transform that permit representing the irradiance in a simple form in terms of the partial derivatives of the wavefront error. Additionally, we briefly describe from this point of view a methodology for the quantitative analysis of the test.

Leukocoria in a 4-year-old boy.

A healthy 4-year-old boy referred for evaluation of an abnormal red reflex in the left eye was noted, on fundus examination, to have extensive white, striated lesions surrounding the optic nerve that involved the superior and inferior macular arcades. On further examination, he was found to have ipsilateral high myopia and amblyopia. The triad of unilateral myelinated retinal nerve fibers, myopia, and amblyopia led to a diagnosis of Straatsma syndrome, which requires early treatment to prevent permanent vision loss. Treatment comprised a contact lens for refractive correction of the left eye, patching of the right eye, and full-time polycarbonate protective lenses. With 2 years' follow-up, the left eye failed to improve appreciably.

Prolonged hypotony maculopathy following uneventful strabismus surgery.

Hypotony is a rare postoperative complication of strabismus surgery. Resolution has been reported to occur within 1 month of surgery. Here, we describe the case of a 14-year-old boy with prolonged hypotony maculopathy following uneventful bilateral medial rectus recession. The hypotony resolved without long-term sequela after 7 months of treatment with topical steroids and atropine. Ultrasound biomicroscopy revealed a ciliary body effusion, which we hypothesize was the cause of decreased aqueous humor production and hypotony.

Longitudinal Assessment of Macular Thickness and Microvascular Changes in Children with Sickle Cell Disease.

PURPOSE: To longitudinally assess macular thickness and microvascular changes in children with sickle cell disease (SCD). DESIGN: A retrospective consecutive series. SUBJECTS: Children with SCD aged ≤ 18 years who had an ophthalmic examination at Boston Children's Hospital between January 1998 and August 2022. METHODS: Qualitative and quantitative analyses of both OCT and OCT angiography (OCTA) images were performed. MAIN OUTCOME MEASURES: Total retinal thickness measured on macular OCT, superficial capillary plexus and deep capillary plexus (DCP) vessel density (VD), and foveal avascular zone (FAZ) area measured on 6- × 6-mm OCTA scans. RESULTS: International Classification of Diseases, 10th Revision, code search identified 303 pediatric SCD patients who underwent ophthalmic examination during the study period. OCT and OCTA images were acquired on 104 (17.2%) and 60 (9.9%) eyes at presentation and on 159 (26.2%) and 100 (16.5%) eyes at final visit, respectively. Overall, temporal retinal thinning was noted qualitatively in 35.6% of SCD patients at presentation and 39.6% at final visit. Of those patients with macular thinning, 94.6% and 90.5% had peripheral sickle cell retinopathy (SCR) at presentation and final visit. On quantitative OCT analysis, HbSS eyes had a lower retinal thickness in the fovea and temporal parafovea compared with HbSC (P < 0.05). Eyes with peripheral SCR had a larger FAZ at presentation compared with eyes without peripheral SCR (P = 0.004), a lower DCP VD at final visit in the inferior temporal macula (P = 0.03), and a higher DCP VD at final visit in the superior nasal macula (P = 0.01). Eighty eyes of 40 patients had OCT, and 34 eyes of 20 patients had both OCT and OCTA images acquired at both initial and final visits. At final visit, retinal thickness decreased at the fovea, inferior perifovea, and temporal perifovea compared with presentation (P < 0.05). In parallel, VD DCP in the superonasal quadrant increased at final visit (P = 0.03). CONCLUSIONS: Macular retinal thinning was progressive and observed in eyes with and without peripheral SCR. Over time, there was a compensatory increase in DCP VD in the nasal macula on OCTA. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Association of Neighborhood Opportunity With Severity of Retinoblastoma at Presentation.

PURPOSE: To examine the relationship between the Child Opportunity Index (COI) and severity of retinoblastoma at presentation. DESIGN: Cross-sectional study. METHODS: Children (age <18 years) treated for retinoblastoma at a tertiary care center between January 2000 and May 2023 were included. Residential census tract was used to determine the overall and domain-specific COI score for each child. Collected variables included age, sex, race/ethnicity, insurance type, and the International Classification of Retinoblastoma (ICRB) Group at initial examination. The primary outcome was Group D or E retinoblastoma at presentation. Mixed effects regression models were used to estimate the association of COI scores with disease severity at presentation. RESULTS: This study included 125 children (51.2% male). Median age at diagnosis was 13 months (IQR, 5-24 months). One hundred nine (87.2%) children presented with Group D or E retinoblastoma and 33 (26.4%) resided in low or very low opportunity neighborhoods. Children residing in neighborhoods with low overall COI scores (OR, 1.62; 95% CI, 1.01-2.58; P = .044) and low education COI scores (OR, 1.77; 95% CI, 1.13-2.79; P = .013) were at increased odds of presenting with ICRB Group D or E retinoblastoma after adjusting for individual-level socioeconomic factors. CONCLUSION: Children residing in low opportunity neighborhoods-particularly low education opportunity-more often presented with advanced stage retinoblastoma than children residing in neighborhoods with higher opportunity scores. Efforts to improve preventative vision care and access to eye specialty care for children residing in low-resource areas are needed to reduce existing disparities in retinoblastoma.

Occlusive Retinal Vasculitis in a Pediatric Patient With Kikuchi-Fujimoto Disease and Sickle Cell Trait.

A 13-year-old Black male patient with a history of Kikuchi-Fujimoto disease (KFD) and sickle cell trait presented with acute painless vision loss and no light perception vision (NLP) in his left eye. The examination was indicative of occlusive retinal vasculitis with near total central retinal artery occlusion (CRAO). He was started on oral steroids with dramatic reperfusion and improvement of the retinal hemorrhages. However, his vision remained at NLP. Oral steroids were tapered, and rituximab infusion was initiated. While ocular involvement is uncommon in KFD, vision-limiting complications, such as occlusive retinal vasculitis, ophthalmic artery occlusion, and CRAO can occur. Early systemic immunosuppression is key in achieving rapid remission. [Ophthalmic Surg Lasers Imaging Retina 2024;55:235-239.].

Refractive errors in patients with Bardet Biedl syndrome.

PURPOSE: Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive ciliopathy. Within corneal development, primary cilia serve a critical role. We sought to investigate the association of BBS with corneal astigmatism among a cohort of patients with BBS. METHODS: This was a cross-sectional, retrospective study performed at a pediatric ophthalmology department of a tertiary hospital. The study enrolled 45 patients with genetically confirmed Bardet-Biedl syndrome, encompassing a total of 90 eyes observed from February 2011 to August 2021. Spherical and cylindrical refractive errors and keratometry outcome measures, including diopter (D) values at the flattest and steepest axes, were recorded. Corneal astigmatism of greater than 3D is considered extreme corneal astigmatism based on previously published data. RESULTS: Among 45 patients (M:26; F:19), the mean age was 16.4 ± 8.2 years, and the mean best-corrected visual acuity was 20/60. The most common molecular diagnosis was BBS1, seen in 24 of 45 (53.3%). Among all the patients, the mean spherical refractive error was -2.9 ± 3.8D. The mean cylindrical refractive error was 2.6 ± 1.5D. The mean keratometry values at the flattest axis was 43.5 ± 5.3D (39.4-75.0) and at the steepest axis was 47.2 ± 7.3D(41.5-84.0). Among all the patients with BBS, the mean corneal astigmatism was 3.7 ± 1.0D(0.5-7.1), which is considered extreme. CONCLUSION: A cohort of individuals with BBS demonstrated high corneal astigmatism. These results suggest an association between corneal astigmatism and primary ciliary dysfunction and may assist in clinical management and future therapeutic targets among BBS and other corneal disorders.

The Association of Race, Ethnicity, and Insurance Status with the Visual Acuity of Retinoblastoma Survivors in the IRIS® Registry.

PURPOSE: To identify sociodemographic factors associated with the visual outcomes of retinoblastoma survivors. METHODS: Retrospective cohort study using a US-based clinical data registry. All individuals < 18 years of age with a history of retinoblastoma in the Intelligent Research in Sight (IRIS®) Registry (1/1/2013-12/31/2020). The primary outcome was visual acuity below the threshold for legal blindness (20/200 or worse) in at least one eye. Multivariable logistic regression was used to evaluate the association between visual outcomes and age, sex, laterality, race, ethnicity, type of insurance, and geographic location. RESULTS: This analysis included 1545 children with a history of retinoblastoma. The median length of follow-up was 4.1 years (IQR, 2.2-5.9 years) and the median age at most recent clinical visit was 12 years (IQR, 8-16 years). Retinoblastoma was unilateral in 54% of cases. Poor vision in at least one eye was identified in 78% of all children and poor vision in both eyes in 17% of those with bilateral disease. Poor visual outcomes were associated with unilateral diagnosis (OR, 1.55; 95% CI,1.13-2.12; p = .007), Black race (OR, 2.03; 95% CI, 1.19-3.47; p = .010), Hispanic ethnicity (OR, 1.65; 95% CI, 1.16-2.37; p = .006), and non-private insurance (OR, 1.47; 95% CI, 1.02-2.10; p = .037). CONCLUSIONS: Poor visual outcomes appear to be more common among Black, Hispanic, and publicly insured children with a history of retinoblastoma, raising concerns regarding healthcare inequities. Primary care physicians should ensure that young children receive red reflex testing during routine visits and consider retinoblastoma in the differential diagnosis of abnormal eye exams.

Leukemic infiltration of the ciliary body in a child with T-cell acute lymphoblastic leukemia.

A 14-year-old boy presented after 2 months of vision loss, redness, and pain in the right eye, initially treated as anterior uveitis with topical corticosteroids. He had a 1-year history of T-cell acute lymphoblastic leukemia, which had been in remission for 6 months. On examination, visual acuity in the right eye was light perception, with 4+ anterior chamber cells, pupillary membrane, and an intumescent cataract. Ultrasound biomicroscopy (UBM) revealed a ciliary body mass and capsular bag rupture. After consultation with his oncologist, he received 10 radiotherapy sessions. At 1 month, UBM showed resolution of the mass. After 1 year of remission, the patient underwent pars plana vitrectomy, pupillary membranectomy, and placement of a scleral-fixated intraocular lens. Thirty months after surgery, visual acuity was 20/25. Leukemic infiltration of the ciliary body is a rare manifestation of the disease that is often misdiagnosed as uveitis.

UPL3 Promotes BZR1 Degradation, Growth Arrest, and Seedling Survival under Starvation Stress in Arabidopsis.

BRASSINAZONE RESISTANT 1 (BZR1) is a key transcription factor of the brassinosteroid signaling pathway but also a signaling hub that integrates diverse signals that modulate plant growth. Previous studies have shown that starvation causes BZR1 degradation, but the underlying mechanisms are not understood. Here we performed quantitative proteomic analysis of BZR1 interactome under starvation conditions and identified two BZR1-interacting ubiquitin ligases, BAF1 and UPL3. Compared to the wild type, the upl3 mutants show long hypocotyl and increased BZR1 levels when grown under sugar starvation conditions but not when grown on sugar-containing media, indicating a role of UPL3 in BZR1 degradation specifically under starvation conditions. The upl3 mutants showed a reduced survival rate after starvation treatment, supporting the importance of UPL3-mediated BZR1 degradation and growth arrest for starvation survival. Treatments with inhibitors of TARGET of RAPAMYCIN (TOR) and autophagy altered BZR1 level in the wild type but were less effective in upl3 , suggesting that UPL3 mediates the TOR-regulated and autophagy-dependent degradation of BZR1. Further, the UPL3 protein level is increased posttranscriptionally by starvation but decreased by sugar treatment. Our study identifies UPL3 as a key component that mediates sugar regulation of hormone signaling pathways, important for optimal growth and survival in plants. IN A NUTSHELL: Background: The coordination between signaling pathways that monitor the levels of photosynthate and growth hormones is crucial for optimizing growth and survival, but the underlying mechanisms are not fully understood. When the sugar level is low, the BZR1 transcription factor of the brassinosteroid (BR) signaling pathway is degraded, and hence growth is attenuated to prevent starvation and enhance survival. When sugar is sufficient, sugar signaling inhibits BZR1 degradation and enables BR promotion of plant growth. The key component that mediates starvation-induced BZR1 degradation remains unknown.Question: What proteins interact with BZR1 and mediate its degradation under sugar starvation?Finding: We performed immunoprecipitation mass spectrometry analysis of BZR1 in starvation-treated Arabidopsis and identified many BZR1-interacting proteins, including two E3 ligases UPL3 and BAF1. Genetic analysis showed that UPL3 plays a specific and prominent role in promoting autophagy-dependent BZR1 degradation and plant survival under sugar-starvation conditions.Next step: How sugar-TOR signaling regulates UPL3 level remains to be studied in the future.

A case of Aicardi syndrome associated with duplication event of Xp22 including SHOX.

BACKGROUND: Aicardi syndrome is a neurodevelopmental disorder characterized by a triad of partial or complete agenesis of the corpus callosum, infantile spasms, and pathognomonic chorioretinal lacunae. METHODS: Examination, multimodal imaging, and genetic testing were used to guide diagnosis. RESULTS: We report a case of a pediatric patient who was initially diagnosed with refractory infantile spasms. The patient was unresponsive to conventional antiepileptic therapy, and genetic testing with whole exome and mitochondrial genome sequencing could not identify the underlying cause, so vigabatrin was initiated. The ophthalmic examination under anesthesia for vigabatrin toxicity screening revealed chorioretinal atrophy in the retinal periphery of both eyes, with two 3-disc diameter chorioretinal lacunae superotemporal and inferonasal to the optic nerve in the left eye. Given the neuroimaging findings of corpus callosum hypoplasia with polymicrogyria and ocular findings, the patient was diagnosed with Aicardi syndrome. Genetic testing revealed a novel duplication event at the Xp22 locus. CONCLUSIONS: Aicardi syndrome, albeit a rare condition, should always be considered in the differential diagnosis when investigating a female child with refractory seizures in early childhood. Genetic testing may help further our understanding of AIS and the search for a genetic etiology.

Cytomegalovirus retinitis and immune recovery uveitis in a pediatric patient with leukemia.

Immune recovery uveitis (IRU) is an ocular form of immune reconstitution inflammatory syndrome, which is rare in the pediatric population. We report a case of IRU in an 11-year-old girl with a history of cytomegalovirus (CMV) retinitis in the setting of acute leukemia, who developed uveitis, vitritis, retinitis, and vasculitis during immune reconstitution. She was found to have negative CMV antigenemia, and the disease occurred during concurrent systemic antiviral therapy. Anterior chamber tap confirmed the absence of the CMV in the eye, and recurrent blood samples continued to reveal absent CMV viral particles systemically while her lymphocyte count was steadily increasing. The patient responded to oral steroids, leading to resolution of active retinitis. Tapering the steroids caused a mild reactivation of the ocular immune response.

Semi-Huber potential function for image segmentation.

In this work, a novel model of Markov Random Field (MRF) is introduced. Such a model is based on a proposed Semi-Huber potential function and it is applied successfully to image segmentation in presence of noise. The main difference with respect to other half-quadratic models that have been taken as a reference is, that the number of parameters to be tuned in the proposed model is smaller and simpler. The idea is then, to choose adequate parameter values heuristically for a good segmentation of the image. In that sense, some experimental results show that the proposed model allows an easier parameter adjustment with reasonable computation times.

Combined Hamartoma of the Retina and Retinal Pigment Epithelium in a Patient With Fragile X Syndrome.

A 13-year-old boy with fragile X syndrome presented with painless, decreased vision in his right eye. Funduscopy revealed fibrotic tissue and an epiretinal membrane. This patient with fragile X syndrome was diagnosed as having combined hamartoma of the retina and retinal pigment epithelium and treated with vitrectomy and epiretinal membrane peeling. [J Pediatr Ophthalmol Strabismus. 2022;59(4):e39-e41.].