Ciliary disease

Renal ciliopathies are a group of genetic disorders that affect the function of the primary cilium in the kidney, as well as other organs. Since primary cilia are important for regulation of cell signaling pathways, ciliary dysfunction results in a range of clinical manifestations, including renal failure, cyst formation, and hypertension. We summarize the current understanding of the pathophysiological and pathological features of renal ciliopathies in childhood, including autosomal dominant and recessive polycystic kidney disease, nephronophthisis, and Bardet-Biedl syndrome, as well as skeletal dysplasia associated renal ciliopathies...

OBJECTIVES: Planar cell polarity (PCP) signaling, essential for uniform alignment and directional beating of motile cilia, has been investigated in multiciliated epithelia. As a complex structure connecting the middle ear to the nasopharynx, the eustachian tube (ET) is important in the onset of ear-nose-throat diseases. However, PCP signaling, including the orientation that is important for ciliary motility and clearance function in the ET, has not been studied. We evaluated PCP in the ET epithelium...

BACKGROUND: Glaucoma is a progressive optic neuropathy and it is the main cause of irreversible blindness worldwide. Intraocular pressure (IOP) is the only modifiable one and trabeculectomy is commonly considered the surgical "gold standard" to decrease IOP. In particular cases, other kind of surgeries, as the Ahmed Glaucoma Valve (AGV) implant, are a reliable alternative. Usually, the silicone tube of AGV surgery is inserted into the anterior chamber. Sometimes it is necessary to place the AGV silicone tube in the ciliary sulcus, especially in cases of endothelial decompensation...

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite 70% of Puerto Rican patients having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c...

BACKGROUND: Nonspecific orbital inflammation (NSOI) represents a perplexing and persistent proliferative inflammatory disorder of idiopathic nature, characterized by a heterogeneous lymphoid infiltration within the orbital region. This condition, marked by the aberrant metabolic activities of its cellular constituents, starkly contrasts with the metabolic equilibrium found in healthy cells. Among the myriad pathways integral to cellular metabolism, purine metabolism emerges as a critical player, providing the building blocks for nucleic acid synthesis, such as DNA and RNA...

UNLABELLED: Primary ciliary dyskinesia (PCD) is a rare disorder characterized by extensive genetic heterogeneity. However, in the genetic pathogenesis of PCD, copy number variation (CNV) has not received sufficient attention and has rarely been reported, especially in China. Next-generation sequencing (NGS) followed by targeted CNV analysis was used in patients highly suspected to have PCD with negative results in routine whole-exome sequencing (WES) analysis. Quantitative real-time polymerase chain reaction (qPCR) and Sanger sequencing were used to confirm these CNVs...

The carboxy-terminus of the spliceosomal protein PRPF8, which regulates the RNA helicase Brr2, is a hotspot for mutations causing retinitis pigmentosa-type 13, with unclear role in human splicing and tissue-specificity mechanism. We used patient induced pluripotent stem cells-derived cells, carrying the heterozygous PRPF8 c.6926 A > C (p.H2309P) mutation to demonstrate retinal-specific endophenotypes comprising photoreceptor loss, apical-basal polarity and ciliary defects. Comprehensive molecular, transcriptomic, and proteomic analyses revealed a role of the PRPF8/Brr2 regulation in 5'-splice site (5'SS) selection by spliceosomes, for which disruption impaired alternative splicing and weak/suboptimal 5'SS selection, and enhanced cryptic splicing, predominantly in ciliary and retinal-specific transcripts...

PURPOSE: We aimed to examine the correlation between clinical characteristics and the pathogenic gene variants in patients with Primary Ciliary Dyskinesia (PCD). METHODS: We conducted a retrospective single-center study in patients with PCD followed at the University Hospitals Leuven. We included patients with genetically confirmed PCD and described their genotype, data from ultrastructural ciliary evaluation and clinical characteristics. Genotype/phenotype correlations were studied in patients with the most frequently involved genes...

OBJECTIVES: To evaluate the clinical outcomes of chemical ciliary body ablation (CBA) in dogs with chronic glaucoma and concurrent anterior lens luxation and to investigate adverse ocular effects of this procedure. PROCEDURES: Retrospective review of 17 dogs (18 eyes) with chronic glaucoma and concurrent anterior lens luxation treated with intravitreal gentamicin with or without dexamethasone sodium phosphate or triamcinolone acetonide. Data collected included signalment, concurrent ocular disease, topical medications prescribed, follow-up duration, and intraocular pressure (IOP) pretreatment, posttreatment, and at the last follow-up visit...

The ciliary body, located at the junction of the choroid and iris, is crucial in the development of the embryonic eye. Notch2 signalling, Wnt signalling, transforming growth factor β (TGF-β) signalling, and Pax6 signalling are critical for coordinating the ciliary body formation. These signalling pathways are coordinated with each other and participate in the ciliary body development, ensuring the precise formation and optimal functioning of the eye structure. Although rare, ciliary body hypoplasia, ciliary tumours, and genetic-related iritis indicate the intricate nature of ciliary body development...

Aberrant regeneration occurs in forms of oculomotor motor nerve palsy and frequently involves the pupil, but the incidence and functional impact of ciliary muscle involvement in pediatric patients is sparsely reported in the literature. A 4-year-old girl presented with inflammatory oculomotor motor nerve paresis affecting the inferior division. Initial treatment focused on her inability to accommodate through her physiologic +2.5 D hyperopia and the prevention and treatment of amblyopia. She subsequently developed aberrant regeneration of the pupil, with miosis on adduction...

INTRODUCTION: Early-onset severe obesity is usually the result of an underlying genetic disorder, and several genes have recently been shown to cause syndromic and nonsyndromic forms of obesity. The " centrosomal protein 19 ( CEP19 ) " gene encodes for a centrosomal and ciliary protein. Homozygous variants in the CEP19 gene are extremely rare causes of early-onset severe monogenic obesity. Herein, we present a Turkish family with early-onset severe obesity with variable features. METHODS: Sanger sequencing and whole-exome sequencing were performed to identify the genetic etiology in the family...

OBJECTIVES: To determine rates and risk factors of pediatric otitis media (OM) using real-world electronic health record (PEDSnet) data from January 2009 through May 2021. STUDY DESIGN: Retrospective cohort study. SETTING: Seven pediatric academic health systems that participate in PEDSnet. METHODS: Children <6 months-old at time of first outpatient, Emergency Department, or inpatient visit were included and followed longitudinally...

Cilia are fascinating organelles that act as cellular antennae, sensing the cellular environment. Cilia gained significant attention in the late 1990s after their dysfunction was linked to genetic diseases known as ciliopathies. Since then, several breakthrough discoveries have uncovered the mechanisms underlying cilia biogenesis and function. Like most cells in the animal kingdom, neurons also harbor cilia, which are enriched in neuromodulatory receptors. Yet, how neuronal cilia modulate neuronal physiology and animal behavior remains poorly understood...

UNLABELLED: The increasing lens vault (LV) and lens thickness (LT) is a recognized mechanism for primary angle closure glaucoma (PACG). Zonulopathy, causing the abnormal lens position, is an important factor in this mechanism. Several anatomically distinct sets of zonular fibers are present in primate eyes, including ciliary zonules, vitreous zonules and attachments between the posterior insertion zone of the vitreous zonules and the posterior lens equator (PVZ INS-LE strands). Zonulopathy, as a clinical diagnosis, exhibits zonular laxity and loss, long anterior lens zonules (LAZ)...

INTRODUCTION: Fibrous dysplasia is a disorder in which normal bone is gradually replaced by immature fibro-osseous tissue, with an incidence of less than 7% of all benign bone tumors. The management of this disease is a challenge for plastic surgeons and neurosurgeons. GOAL: To describe the diagnostic, therapeutic, and outcome approach of patients with craniofacial fibrous dysplasia seen at the Plastic Surgery Service of the Hospital San José in Bogotá, Colombia...

Motile cilia have essential cellular functions in development, reproduction, and homeostasis. Genetic causes for motile ciliopathies have been identified, but the consequences on cellular functions beyond impaired motility remain unknown. Variants in CCDC39 and CCDC40 cause severe disease not explained by loss of motility. Using human cells with pathological variants in these genes, Chlamydomonas genetics, cryo-electron microscopy, single cell RNA transcriptomics, and proteomics, we identified perturbations in multiple cilia-independent pathways...

Glaucoma is a blinding disease. Reduction of intraocular pressure (IOP) is the mainstay of treatment, but current drugs show side-effects or become progressively ineffective, highlighting the need for novel compounds. We have synthesized a family of perhydro-1,4-oxazepine derivatives of digoxin, the selective inhibitor of Na,K-ATPase. The cyclobutyl derivative (DcB) displays strong selectivity for the human a2 isoform and potently reduces IOP in rabbits. These observations appeared consistent with a hypothesis that in ciliary epithelium DcB inhibits the a2 isoform of Na,K-ATPase, which is expressed strongly in non-pigmented cells, reducing aqueous humor (AH) inflow...

Hydroxyproline-rich glycoproteins (HRGPs) are a ubiquitous class of protein in the extracellular matrices and cell walls of plants and algae, yet little is known of their native structures or interactions. Here, we used electron cryomicroscopy (cryo-EM) to determine the structure of the hydroxyproline-rich mastigoneme, an extracellular filament isolated from the cilia of the alga Chlamydomonas reinhardtii. The structure demonstrates that mastigonemes are formed from two HRGPs (a filament of MST1 wrapped around a single copy of MST3) that both have hyperglycosylated poly(hydroxyproline) helices...

The intraflagellar transport (IFT) machinery plays a crucial role in the bidirectional trafficking of components necessary for ciliary signaling, such as the Hedgehog, Wnt/PCR, and cAMP/PKA systems. Defects in some components of the IFT machinery cause dysfunction, leading to a wide range of human diseases and developmental disorders termed ciliopathies, such as nephronophthisis. The IFT machinery comprises three sub-complexes: BBsome, IFT-A, and IFT-B. The IFT protein 54 (IFT54) is an important component of the IFT-B sub-complex...