The Effectiveness of Partial Lid Margin Excision Including Hair Follicles in Diffuse Trichiasis and Distichiasis

Purpose: In the present study, we introduced and evaluated the effectiveness of partial lid margin excision including hair follicles in diffuse trichiasis and distichiasis. Methods: A retrospective review of medical records was performed on 21 eyelids of 14 patients with diffuse trichiasis and distichiasis. The patients had trichiasis of more than 1/3 of the eyelid margin and received lid margin excision including hair follicles at our hospital. The patients were followed up for more than 3 months after surgical correction. A telephone survey of the surgical outcomes, including recurrence and cosmetic satisfaction, was conducted for patients who were unable to visit the clinic. Success was defined as complete resolution of symptoms, no recurrence of abnormal cilia, and acceptable cosmesis. Results: The patients included five males (6 eyes) and nine females (15 eyes) with an average age of 61.9 years (range, 39.8-82.4 years). The surgical success rate was 90.5%. Two eyelids showed a recurrence of trichiasis requiring additional electrolysis treatment, and one eyelid exhibited skin pigmentation. Conclusions: For patients with diffuse trichiasis and distichiasis, partial lid margin excision including hair follicles showed excellent results with respect to resolving irritating symptoms, with minimal complications, low recurrence, and an easy procedure.

Primary Cilia–Related Pathways Moderate the Development and Therapy Resistance of Glioblastoma

As microtubule-based structures, primary cilia are typically present on the cells during the G0 or G1-S/G2 phase of the cell cycle and are closely related to the development of the central nervous system. The presence or absence of this special organelle may regulate the central nervous system tumorigenesis (e.g., glioblastoma) and several degenerative diseases. Additionally, the development of primary cilia can be regulated by several pathways. Conversely, primary cilia are able to regulate a few signaling transduction pathways. Therefore, development of the central nervous system tumors in conjunction with abnormal cilia can be regulated by up- or downregulation of the pathways related to cilia and ciliogenesis. Here, we review some pathways related to ciliogenesis and tumorigenesis, aiming to provide a potential target for developing new therapies at genetic and molecular levels.

Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by Ectopic Signaling

A single primary cilium projects from most vertebrate cells to guide cell fate decisions. A growing list of signaling molecules is found to function through cilia and control ciliogenesis, including the fibroblast growth factor receptors (FGFR). Aberrant FGFR activity produces abnormal cilia with deregulated signaling, which contributes to pathogenesis of the FGFR-mediated genetic disorders. FGFR lesions are also found in cancer, raising a possibility of cilia involvement in the neoplastic transformation and tumor progression. Here, we focus on FGFR gene fusions, and discuss the possible mechanisms by which they function as oncogenic drivers. We show that a substantial portion of the FGFR fusion partners are proteins associated with the centrosome cycle, including organization of the mitotic spindle and ciliogenesis. The functions of centrosome proteins are often lost with the gene fusion, leading to haploinsufficiency that induces cilia loss and deregulated cell division. We speculate that this complements the ectopic FGFR activity and drives the FGFR fusion cancers.

MIP-T3 Expression Associated with Defects of Ciliogenesis in Airway of COPD Patients

Introduction. Some studies have found that cilia were shorter in COPD smokers than in nonsmokers or healthy smokers. However, the structural abnormalities of cilia and the cause of such abnormalities in COPD patients still remain unknown. Tumor necrosis factor alpha receptor 3 interacting protein 1 (MIP-T3) may play an important role in the progress of ciliary protein transporting. Objectives. This study aimed at exploring the dominated structural abnormalities of cilia and the involvement of MIP-T3 in the pathogenesis of cilia of COPD patients. Methods. Patients who accepted pulmonary lobectomy were divided into 3 groups: the chronic obstructive pulmonary disease (COPD) smoker group, the healthy smoker group, and the nonsmoker group, according to smoking history and pulmonary function. The ultrastructure of cilia and the percentage of abnormal cilia were analyzed using a transmission electron microscope. Real-time PCR, immunohistochemical staining, and western blotting in bronchial epithelium were used to determine MIP-T3 mRNA and protein expression. The relationship between the percentage of abnormal cilia and lung function and MIP-T3 protein expression was analyzed. Results. Patients in the COPD smoker group had increased percentage of abnormal cilia comparing to both the healthy smoker group and the nonsmoker group (both P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (P value <0.05). Moreover, the percentage of abnormal cilia was negatively correlated with FEV1, FEV1/FVC ratio, and FEV1%pred (all P values <0.05). Moreover, the MIP-T3 protein expression was positively correlated with the percentage of abnormal cilia (P value <0.05). Conclusions. Our results suggested that the abnormal ciliary ultrastructure, which was common in COPD patients, might be due to MIP-T3 downregulation.

Primary cilium and glioblastoma

Glioblastoma (GBM) represents the most common, malignant and lethal primary brain tumour in adults. The primary cilium is a highly conserved and dynamic organelle that protrudes from the apical surface of virtually every type of mammalian cell. There is increasing evidence that abnormal cilia are involved in cancer progression, since primary cilia regulate cell cycle and signalling transduction. In this review, we summarize the role of primary cilium specifically with regard to GBM, where there is evidence postulating it as a critical mediator of GBM tumorigenesis and progression. This opens the way to the application of cilia-targeted therapies (‘ciliotherapy’) as a new approach in the fight against this devastating tumour.

Abstract P260: Role of Primary Endothelial Cilia in Hypertension

Primary cilia are mechanosensory organelles that are projected into the lumen of blood vessels. It has been demonstrated that vascular endothelia require primary cilia to sense and transmit external mechanical stimuli into internal biochemical reactions. One of these reactions includes the biosynthesis and release of nitric oxide, which is one of the most potent endogenous vasodilators. This idea has only been investigated in cultured endothelial cells in vitro . Based on this finding, however, a very bold hypothesis is formed to test that abnormal cilia function results in vascular hypertension. Our laboratory has recently generated and obtained several conditional mouse models to specifically study the function and structure of primary cilia in vascular endothelia. These models include 1) mice without cilia function ( Pkd1 or Pkd2 ); 2) mice without cilia structure ( Tg737 or Kif3a ). Our data indicate that mice with abnormal cilia function ( Pkd1 ) or structure ( Tg737 ) show significantly higher systolic (150±19 for Pdgfbcre:Pkd1 flox/flox and 147±10 for Tie2Cre:Tg737 flox/flox vs. 128±9 for wild-type) and diastolic (120±21 for Pdgfbcre:Pkd1 flox/flox and 120±11 for Tie2Cre:Tg737 flox/flox vs. 102±7 for wild-type) blood pressure than the corresponding wild-type mice. Because there is a positive and continuous correlation between blood pressure and cardiovascular diseases, satellite hypotheses are developed to look at the pathophysiological roles of endothelial cilia in cardiac functions and focal vascular diseases in vivo . Our data clearly point towards deteriorating phenotypes in the cardiac muscle, including cardiac fibrosis due to an increased cardiac workload. As a result, a heart-to-body weight ratio was significantly increased by 17 weeks old (0.008 PdgfbCre;Pkd1 f/f vs. 0.006 Pkd1 f/f ).The present study will very likely provide new insights for hypertension and offer advanced scientific understanding of vascular endothelial cilia in other cardiovascular diseases.

Intraspinal Endodermal Cyst: Ultrastructural Study of Abnormal Cilia

Abnormal cilia were demonstrated in the lining epithelial cells of three cases of intraspinal endodermal (bronchogenic) cyst. The changes comprised a wide spectrum of ultrastructural abnormalities, including (a) cilia with abnormal axonemal microtubules, (b) swollen cilia, (c) compound cilia with or without excessive ciliary matrix, (d) naked cilia without limiting membrane, and (e) intracytoplasmic cilia and aggregates of microtubules. Of these, compound cilia and swollen cilia were most common. Cilia with dynein arm deficiency were not observed. Ciliary abnormalities found in the present study were very similar to those described in the bronchial epithelium of various diseases. The present findings suggest that the lining epithelium of intraspinal endodermal cyst shares similar ciliogenesis and susceptibility to abnormal ciliary formation as that of the bronchial epithelium.

Intraspinal Bronchogenic Cyst: Ultrastructural Study of Abnormal Cilia

Intraspinal cyst formed of tissue proper to the tracheobronchial tract has been referred to as bronchogenic cyst. Six cell types of the cyst epithelium have been identified, i.e., ciliated cells, non-ciliated cells, goblet cells, basal cells, Kulchitsky's cells and undifferentiated cells. This report described the detailed morphological alterations of cilia of the lining epithelium of three cases of intraspinal bronchogenic cyst and compared the findings with the ciliary abnormalities of the tracheobronchial epithelium.Ultrastructural abnormalities of cilia of the intraspinal bronchogenic cyst could be classified into five categories:(A)Cilia showing addition, deletion or disorganization of axonemal minotubules.(B)Swollen cilia containing a single axoneme in an excess amount of matrix: (a) normal 9 + 2 axoneme,(b) stretched axoneme bending toward one side, (c) abnormal axonemal pattern.(C)Compound cilia with multiple axonemal microtubules ensheathed by a common ciliary membrane: (a) two or more normal 9 + 2 axonemes, (b) two or more normal 9 + 2 axonemes sharing doublets, (c) giant compound cilia with numerous normal and abnormal axoneme in random orientation, (d) compound cilia containing cytoplasmic organelles, (e) compound cilia with excessive matrix.

Chronic Lung Disease in Canadian Aboriginal Children Is Not Caused by Abnormal Cilia

BACKGROUND: It has been suggested that abnormalities of the airway cilia are responsible for some of the increased prevalence of bronchiectasis among the Polynesian population of New Zealand.OBJECTIVE: To determine whether abnormalities of the ciliary axoneme were present in Cree children with recurrent pneumonia.DESIGN: Retrospective identification of Cree children under 18 years of age with three or more documented episodes of pneumonia, at least one of which was severe enough to require hospitalization. Physical examination and nasal brushing for ciliary ultrastructure were performed on those who consented to participate in the study.SETTING: Out-patient department of Moose Factory General Hospital, the referral hospital for the James Bay Region of Northern Ontario.PATIENTS: Ten children (seven males; three females) met the diagnostic criteria and lived in Moose Factory or Moosonee. Six patients (five boys, one girl, mean age 7 years 2 months) consented to examination and nasal brushing.RESULTS: Although the percentage of abnormal cilia (21%) was three to seven times greater than that reported for the control population, the abnormalities seen were characteristic of acquired axonemal defects rather than primary ciliary dyskinesia.CONCLUSIONS: In this population, recurrent pneumonia did not appear to be associated with congenital defects of the ciliary axoneme (primary ciliary dyskinesia). This is consistent with a review of published transmission electron microscopy studies of nasal cilia from the Maori of New Zealand.