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2021 ◽  
Vol 9 ◽  
Author(s):  
Yao Li ◽  
Yuxing Li ◽  
Xi Liu ◽  
Yonghong He ◽  
Tian Guan

Purpose: The aims of the study were to investigate cellular mechanisms of cold cataract in young lenses of wild-type C57BL/6J (B6WT) mice treated at different temperatures and to test a hypothesis that cold cataract formation is associated with the changes in lens protein and water distribution at different regions across lens fiber cells by Raman spectroscopy (RS).Methods: RS was utilized to scan the mouse lens at different regions with/without cold cataract. Three regions with various opacification along the equatorial axis in the anterior–posterior lens section were scanned. The intensity ratio of Raman bands at 2,935 and 3,390 cm−1 (Ip/Iw) were used to evaluate lens protein and water distribution. We further determined water molecular changes through Gaussian profiles of water Raman spectra.Results: Three specific regions 1, 2, and 3, located at 790–809, 515–534, and 415–434 μm away from the lens center, of postnatal day 14 B6WT lenses, were subjected to RS analysis. At 37°C, all three regions were transparent. At 25°C, only region 3 became opaque, while at 4°C, both regions 2 and 3 showed opacity. The sum of the difference between Ip/Iw and the value of linear fitting line from scattered-line at each scanning point was considered as fluctuation degree (FD) in each region. Among different temperatures, opaque regions showed relatively higher FD values (0.63 and 0.79 for regions 2 and 3, respectively, at 4°C, and 0.53 for region 3 at 25°C), while transparent regions provided lower FD values (less than 0.27). In addition, the decrease in Gaussian peak II and the rising of Gaussian peak III and IV from water Raman spectra indicated the instability of water molecule structure in the regions with cold cataract.Conclusion: Fluctuation degrees of RS data reveal new mechanistic information about cold cataract formation, which is associated with uneven distribution of lens proteins and water across lens fiber cells. It is possible that RS data partly reveals cold temperature-induced redistribution of lens proteins such as intermediate filaments in inner fiber cells. This lens protein redistribution might be related to unstable structure of water molecules according to Gaussian profiles of water RS.


2021 ◽  
Vol 212 ◽  
pp. 108768
Author(s):  
Wyndham More Batchelor ◽  
Bianca Maceo Heilman ◽  
Esdras Arrieta-Quintero ◽  
Marco Ruggeri ◽  
Jean-Marie Parel ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shahid Y. Khan ◽  
Muhammad Ali ◽  
Yura Jang ◽  
Taekyung Ryu ◽  
Andrew J. Schwab ◽  
...  

AbstractHere, we report a multi OMIC (transcriptome, proteome, and metabolome) approach to investigate molecular changes in lens fiber cells (FC) of mice exposed to cigarette smoke (CS). Pregnant mice were placed in a whole-body smoke chamber and a few days later pups were born, which were exposed to CS for 5 hours/day, 5 days/week for a total of 3½ months. We examined the mice exposed to CS for CS-related cataractogenesis after completion of the CS exposure but no cataracts were observed. Lenses of CS-exposed and age-matched, untreated control mice were extracted and lens FC were subjected to multi OMIC profiling. We identified 348 genes, 130 proteins, and 14 metabolites exhibiting significant (p < 0.05) differential levels in lens FC of mice exposed to CS, corresponding to 3.6%, 4.3%, and 5.0% of the total genes, protein, and metabolites, respectively identified in this study. Our multi OMIC approach confirmed that only a small fraction of the transcriptome, the proteome, and the metabolome was perturbed in the lens FC of mice exposed to CS, which suggests that exposure of CS had a minimal effect on the mouse lens. It is worth noting that while our results confirm that CS exposure does not have a substantial impact on the molecular landscape of the mouse lens FC, we cannot rule out that CS exposure for longer durations and/or in combination with other morbidities or environmental factors would have a more robust effect and/or result in cataractogenesis.


2021 ◽  
Author(s):  
Qian Gao ◽  
Hao Xu ◽  
Yuping Duan ◽  
Leiming Cai ◽  
Zhiwen Nie ◽  
...  

Abstract Background: Currently, there is little information on the expression profiles of circRNAs in the lens. βB2-crystallin (CRYBB2) is an abundant protein in the mammalian lens, and its abnormal expression contributes to the development of cataract. This study aimed at exploring how Crybb2 knockout could modulate the expression profiles of circRNAs in mouse lens. Methods and Results: We extracted total RNAs from the lens of wide-type (WT) and Crybb2 -/- mice and after depleted their rRNAs and broken the remaining RNAs, we reversely transcribed the RNAs into cDNAand sequenced them. Furthermore, we performed bioinformatics to identify and analyze the differentially expressed circRNAs and predicted their potential functions. We validated some differentially expressed circRNAs by quantitative RT-PCR. We employed RNA-seq to identify 49,494 circRNAs and compared to the WT lens, 149 circRNAs were upregulated and 172 downregulated in Crybb2 -/- mouse lens. With the top 300 miRNA-circRNA interaction pairs, we constructed a network of circRNA-miRNA interactions. Moreover, those differentially expressed circRNAs participated in various biological processes, such as lens fiber cell development, calcium channel complex, structural constituent of the lens. They were involved in several important pathways, such as the canonical Wnt signaling pathway. Quantitative RT-PCR validated some differently expressed circRNAs in the lens of Crybb2 -/- mice. Conclusions: Crybb2 knockout significantly modulated circRNA expression profiles in the lens of mice, which may help clarify the roles of circRNAs in age-related cataracts.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hélène Choquet ◽  
Ronald B. Melles ◽  
Deepti Anand ◽  
Jie Yin ◽  
Gabriel Cuellar-Partida ◽  
...  

AbstractCataract is the leading cause of blindness among the elderly worldwide and cataract surgery is one of the most common operations performed in the United States. As the genetic etiology of cataract formation remains unclear, we conducted a multiethnic genome-wide association meta-analysis, combining results from the GERA and UK Biobank cohorts, and tested for replication in the 23andMe research cohort. We report 54 genome-wide significant loci, 37 of which were novel. Sex-stratified analyses identified CASP7 as an additional novel locus specific to women. We show that genes within or near 80% of the cataract-associated loci are significantly expressed and/or enriched-expressed in the mouse lens across various spatiotemporal stages as per iSyTE analysis. Furthermore, iSyTE shows 32 candidate genes in the associated loci have altered gene expression in 9 different gene perturbation mouse models of lens defects/cataract, suggesting their relevance to lens biology. Our work provides further insight into the complex genetic architecture of cataract susceptibility.


2021 ◽  
pp. 108676
Author(s):  
Adam P. Faranda ◽  
Mahbubul H. Shihan ◽  
Yan Wang ◽  
Melinda K. Duncan
Keyword(s):  

2021 ◽  
pp. 108663
Author(s):  
Adam P. Faranda ◽  
Mahbubul H. Shihan ◽  
Yan Wang ◽  
Melinda K. Duncan
Keyword(s):  

2021 ◽  
Vol 197 (1) ◽  
Author(s):  
B. Tanno ◽  
G. Babini ◽  
S. Leonardi ◽  
I. De Stefano ◽  
C. Merla ◽  
...  

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