RPGR and RP2: targets for the treatment of X-linked retinitis pigmentosa?

Retinitis pigmentosa is the most important hereditary eye disease and there is currently no cure available. Although mutations were found in more than 40 genes in patients with retinitis pigmentosa, only two genes have thus far been found to be responsible for one of the most severe forms of the disease, X-linked retinitis pigmentosa. In this review, we highlight the current knowledge about the two gene products RPGR and RP2 and try to link genetic data from patients with functional data on the corresponding proteins. Based on the fact that recent gene therapeutic approaches for eye diseases are at a very promising stage, we discuss the potential of RPGR and RP2 as drug targets to treat retinitis pigmentosa.     

Localization of 5-HT6 receptors at the plasma membrane of neuronal cilia in the rat brain

5-HT₆ receptor-like immunoreactivity has been previously found in association with both neuronal dendrites and cilia in the striatum, nucleus accumbens, olfactory tubercle and islands of Calleja of the rat brain. Using immunogold pre-embedding immunocytochemical techniques to investigate the subcellular localization of 5-HT₆ receptor-like immunoreactivity in cilia, we showed that immunogold particles were associated with their plasma membrane, and not with microtubules. This membrane localization is consistent with a possible physiological role, which is still unknown, of these receptors.     

Case for the Panel

Twenty-two cases displaying potentially precancerous epithelial changes of the bronchial mucosa—including basal and goblet cell hyperplasia, epidermoid metaplasia, and dysplasia—showed a wide variety of cilial abnormalities on the ultrastructural level. The changes comprised abnormal configurations of the ciliary plasma membrane, variations in the amount of ciliary matrix, disorganization of basal bodies, and diverse alterations of the axonemal microtubular pattern. More than one such alteration was observed in one and the same case, and there was no correlation with the actual type of epithelial lesion nor the degree of dysplasia. These changes, interpreted as abnormal ciliary regeneration in severely damaged ciliated cells, are potentially reversible and seem to represent a nonspecific response of the affected cells to an ample spectrum of noxes. Their diagnostic significance is poor, especially with regard to the modification of the axonemal microtubular pattern, unless the entire clinical picture suggests an immotile cilia syndrome.     

不动纤毛综合征的诊断:附3例分析

为探索一种简便易行的不动纤毛综合征诊断方法，对3例反复呼吸道感染患儿进行病因学的诊断。根据患儿病史、症状、体征、特殊检查（纤维支气管镜取支气管粘膜活组织病理检查和鼻粘膜活组织病理检查）及文献资料综合分析，进行病因学诊断，同时比较两种病理资料获取途径的利弊。资料显示，3例患儿中有2例支气管粘膜和鼻粘膜均显示了相同结果，即患儿呼吸道粘膜的纤毛结构异常；1例患儿通过X线摄片、CT、B超等检查，证实存在内脏转位、鼻窦炎、支气管扩张三联征。结果3例患儿均确诊为不动纤毛综合征，其中1例为Kartagener综合征。提示鼻粘膜活检与支气管粘膜活检结果相同，可作为一种简便易行的不动纤毛综合征诊断方法。     

Coexistante of intraocular eyelashes and anterior chamber cyst after penetrating eye injury: a case presentation

We herein describe a patient in whom two intraocular eyelashes and an anterior chamber cyst embedded into the anterior surface of the iris was detected following penetrating eye injury. After a one year asymptomatic period, the patient was hospitalized because of uveitic reaction in the anterior chamber which may be due to cyst development. The lashes and cyst were removed surgically, and examined pathologically. There was no complication in one year follow-up period.     

DAB2IP modulates primary cilia formation associated with renal tumorigenesis

Primary cilium is a microtubule-based organelle that projects from the surfaces of most mammalian cell types and protrudes into the extracellular milieu as an antenna-like sensor to senses extracellular physical and biochemical signals, and then transmits signals into cytoplasm or nucleus to regulate numerous physical and developmental processes. Therefore, loss of primary cilia is associated to multiple cancer progression, including skin, breast, pancreas, ovarian, prostate, and kidney cancers. Our previous studies demonstrate that high prevalent loss of DAB2 Interacting Protein (DAB2IP) is associated with renal cell carcinoma, and we found a kinesin-like protein, kinesin family member 3A (KIF3a), was significantly increased in DAB2IP-interacting protein fraction. KIF3 is one of the most abundant kinesin-2 family proteins expressed in cells, and it is necessary for ciliogenesis. In this study, we observed that loss of DAB2IP in normal kidney epithelial cell significantly impair primary cilia formation. We unveiled a new mechanism of primary cilia stability via DAB2IP and KIF3a physical interaction at DAB2IP-PH domain. Furthermore, we found that KIF3a also act as a tumor suppressor in renal cell carcinoma, affect tumor development and patient survival.     

Nitric oxide levels and ciliary beat frequency in indigenous New Zealand children

New Zealand children's morbidity from respiratory disease is high. This study examines whether subclinical ciliary abnormalities underlie the increased prevalence of respiratory disease in indigenous New Zealand children. A prospective study enrolled a group of healthy children who were screened for respiratory disease by questionnaire and lung function. Skin-prick tests were performed to control for atopy. Exhaled and nasal NO was measured online by a single-breath technique using chemiluminescence. Ciliary specimens were obtained by nasal brushings for assessment of structure and function. The ciliary beat frequency (CBF) (median CBF, 12.5 Hz; range, 10.4-16.8 Hz) and NO values (median exhaled NO, 5.6 ppb; range, 2.3-87.7 ppb; median nasal NO, 403 ppb; range, 34-1,120 ppb) for healthy New Zealand European (n=58), Pacific Island (n=61), and Maori (n=16) children were comparable with levels reported internationally. No ethnic differences in NO, atopy, or CBF were demonstrated. Despite an apparently normal ciliary beat, the percentage of ciliary structural defects was 3 times higher than reported controls (9%; range, 3.6-31.3%), with no difference across ethnic groups. In conclusion, it is unlikely that subclinical ciliary abnormalities underlie the increased prevalence of respiratory disease in indigenous New Zealand children. The high percentage of secondary ciliary defects suggests ongoing environmental or infective damage.     

Brain dysfunction in primary ciliary dyskinesia?

To identify possible altered flow of cerebrospinal fluid due to defective ependymal ciliary motion, 8 subjects, including 6 with Kartagener's syndrome (KS), 1 with primary ciliary dyskinesia (PCD) and 1 with situs inversus were studied by computerized tomography (CT) examination of the brain and paranasal sinuses and had their nasal cilia studied by in vitro ciliary beat frequency (CBF) analysis. Five of the 6 patients with KS and the one with PCD had abnormal CBF (slowed or absent), while the CBF of 1 KS patient and the subject with situs inversus was normal. CT evaluation of the brains of all subjects was normal. Sinus examinations of the 7 patients with KS and PCD revealed mucosal thickening. We conclude that slowed or absent ciliary activity as measured in vitro is not associated with brain abnormalities as demonstrated by CT examination.