Functional characterization of CEP250 variant identified in nonsyndromic retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree of genetic, allelic, and phenotypic heterogeneity. CEP250 encodes the C-Nap1 protein and has been associated with various retinal phenotypes. Here, we report the identification of a mutation (c.562C>T, p.R188*) in the CEP250 in a consanguineous family with nonsyndromic RP. To gain insights into the molecular pathomechanism underlying CEP250 defects and the functional relevance of CEP250 variants in humans, we conducted a functional characterization of CEP250 variant using a novel Cep250 knockin mouse line. Remarkably, the disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations. The homozygous knockin mice showed significantly reduced retinal thickness and ERG responses. This study not only broadens the spectrum of phenotypes associated with CEP250 mutations, but also, for the first time, elucidates the function of CEP250 in photoreceptors using a newly established animal model.

Topographic distribution features of the choroidal and retinal nerve fiber layer thickness in Chinese school-aged children.

AIM: To explore the topographic distribution features of choroidal thickness (CT) and retinal nerve fiber layer thickness (RNFLT), and determine the relationship between CT and ocular parameters in school-aged children. METHODS: The healthy school-aged children with low ametropia or emmetropia in Wenzhou were recruited for this cross-sectional study. With high-density optical coherence tomography (HD-OCT) combined with MATLAB software, the CT and RNFLT values in the macular area were measured at different locations and compared. Statistical analyses were performed to evaluate the correlation between CT and ophthalmic parameters, such as spherical equivalent (SE) and the axial length (AL). RESULTS: A total of 279 school-aged children with 8.00±1.35 years of mean age (range, 6-10y) were included. The mean AL was 23.66±0.86 mm. The mean CT in CT-C (264.31±48.93 µm) was thicker than that in CT-N1 (249.54±50.52 µm), and the average CT in the parafoveal region was also thicker than that in CT-N2 (235.65±50.63 µm). The subfoveal CT also varied substantially across refractive errors (P<0.001), and those with myopia (250.59±47.01 µm) exhibited a thinner choroid compared with those with emmetropia (278.74±48.06 µm). CT negatively correlated with AL (y=-21.72x+779.17; R 2=0.1458), and positively correlated with SE (y=15.76x+271.9; R 2=0.0727, OD; y=18.31x+269.8; R 2=0.1007, OS). The average RNFLT was thickest in the peripapillary region (236.35±19.03 µm), the mean RNFLT-S (131.10±15.16 µm) was thicker than the RNFLT-I (128.20±16.59 µm), and the mean RNFLT-T (76.54±11.99 µm) was thicker than the RNFLT-N (64.28±8.55 µm). The variations in the RNFLT between quadrants did differ between those with myopia and emmetropia (P<0.05). CONCLUSION: We establish demographic information for the choroid and RNFLT. These findings provide information that should be considered in future analyses of the CT and RNFLT in OCT studies in school-aged children.

Topographic distribution features of the choroidal and retinal nerve fiber layer thickness in Wenzhou school-aged children.

AIM: To explore the topographic distribution features of choroidal thickness (CT) and retinal nerve fiber layer thickness (RNFLT), and determine the relationship between CT and ocular parameters in school-aged children. METHODS: The healthy school-aged children with low myopia or emmetropia in Wenzhou were recruited for this cross-sectional study. With high-density optical coherence tomography (HD-OCT) combined with MATLAB software, the CT and RNFLT values in the macular area were measured at different locations and compared. Statistical analyses were performed to evaluate the correlation between CT and ophthalmic parameters, such as spherical equivalent (SE) and the axial length (AL). RESULTS: A total of 279 school-aged children with 8.00±1.35 years of mean age (range, 6-10y) were included. The mean AL was 23.66±0.86 mm. The mean CT in CT-C (264.31±48.93 µm) was thicker than that in CT-N1 (249.54±50.52 µm), and the average CT in the parafoveal region was also thicker than that in CT-N2 (235.65±50.63 µm). The subfoveal CT also varied substantially across refractive errors (P<0.001), and those with myopia (250.59±47.01 µm) exhibited a thinner choroid compared with those with emmetropia (278.74±48.06 µm). CT positively correlated with AL (y=11.12x-4.15; R 2=0.18), and positively correlated with SE (y=90.07x+17.916; R 2=14.2). The average RNFLT was thickest in the peripapillary region (236.35±19.03 µm), the mean RNFLT-S (131.10±15.16 µm) was thicker than the RNFLT-I (128.20±16.59 µm), and the mean RNFLT-T (76.54±11.99 µm) was thicker than the RNFLT-N (64.28±8.55 µm). The variations in the RNFLT between quadrants did differ between those with myopia and emmetropia (P<0.05). CONCLUSION: We establish demographic information for the choroid and RNFLT. These findings provide information that should be considered in future analyses of the CT and RNFLT in OCT studies in school-aged children.

Ablation of Mature miR-183 Leads to Retinal Dysfunction in Mice.

Purpose: The microRNA cluster miR-183C, which includes miR-183 and two other genes, is critical for multiple sensory systems. In mouse retina, removal of this cluster results in photoreceptor defects in polarization, phototransduction, and outer segment elongation. However, the individual roles of the three components of this cluster are not clearly known. We studied the separate role of mouse miR-183 in in vivo. Methods: miR-183 knockout mice were generated using the CRISPR/Cas9 genome-editing system. Electroretinography were carried out to investigate the changes of retinal structures and function. miR-183 was overexpressed by subretinal adeno-associated virus (AAV) injection in vivo. Rnf217, a target of miR-183 was overexpressed by cell transfection of the photoreceptor-derived cell line 661W in vitro. RNA sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to compare the gene expression changes in AAV-injected mice and transfected cells. Results: The miR-183 knockout mice showed progressively attenuated electroretinogram responses. Over- or under-expression of Rnf217, a direct target of miR-183, misregulated expression of cilia-related BBSome genes. Rnf217 overexpression also led to compromised electroretinography responses in WT mice, indicating that it may contribute to functional abnormalities in miR-183 knockout mice. Conclusions: miR-183 is essential for mouse retinal function mediated directly and indirectly through Rnf217 and cilia-related genes. Our findings provide valuable insights into the explanation and analysis of the regulatory role of the individual miR-183 in miR-183C.

[Application of extreme value distribution theory in the forecast of chilling return periods of Guangdong Province, China.] / 极值分布理论在广东寒害重现期预测中的应用.

Chilling is the third weather disaster following flood and typhoon in Guangdong Province. Prediction of chilling return period is of practical significance for scientific reduction and protection of disaster. Four models, including Gumbel distribution, Weibull distribution, log-normal distribution and Peasron-III distribution, were applied, based on the chilling index, to fit the probability distribution of chilling extreme calculated by chilling accumulation for 86 weather stations of Guangdong Province from 1961 to 2015 (December to the following February). The optimal models were selected to calculate the chilling extreme value of return periods. Results showed that Pearson-III distribution was the optimal model for 77 out of the 86 weather stations. The log-normal distribution was optimal for eight weather stations and Gumbel distribution was optimal for only one station. Weibull distribution was not suitable for modeling extreme value of Guangdong Province. Different return periods of 10-, 25-, 50- and 100-year were predicted by optimal distribution models respectively, with a relative error less than 6%. Chilling extreme for years presented obviously latitude distribution feature, with more in north side and less in south side, which matched the distributions of the lowest temperature, average temperature and temperature dipping scale during chilling period. Our results are useful for guiding the chilling defense for relevant industries in Guangdong Province.