The purpose of this study was to identify novel colorectal cancer (CRC)-causing alleles in unexplained familial CRC cases. In order to do so, coding regions in five candidate genes (MGMT, AXIN2, CTNNB1, TGFBR1 and TGFBR2) were sequenced in 11 unrelated microsatellite-stable hereditary non-polyposis CRC (MSS HNPCC) cases. Selected genetic variants were genotyped in a discovery set of 27 MSS HNPCC cases and 85 controls. One genetic variant, rs67687202, in TGFBR1 emerged as significant (P = 0.002), and it was genotyped in a replication set of 87 additional MSS HNPCC-like cases and 338 controls where it was also significantly associated with MSS HNPCC cases (P = 0.041). In the combined genotype data, rs67687202 was associated with a moderate increase in CRC risk (OR = 1.68; 95% CI = 1.13-2.50; P = 0.010). We tested a highly correlated SNP rs868 in 723 non-familial CRC cases compared with 629 controls, and it was not significantly associated with CRC risk (P = 0.370). rs868 is contained in a let-7 miRNA binding site in the 3'UTR of TGFBR1, which might provide a functional basis for the association in MSS HNPCC. In luciferase assays, the risk-associated allele for rs868 was associated with half the luciferase expression in the presence of miRNA let-7b-5p compared with protective allele, suggesting more binding of let-7b-5p and less TGFBR1 expression. Thus, rs868 potentially is a CRC risk-causing allele. Our results support the concept that rs868 is associated with lower TGFBR1 expression thereby increasing CRC risk.
Purpose: To evaluate long-term uveal and capsular biocompatibility of a new fluid-filled modular accommodating intraocular lens (IOL) consisting of base and fluid lenses. Setting: John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA. Design: Experimental study. Methods: Bilateral phacoemulsification was performed on 8 rabbits; 1 eye received the test IOL (Juvene) and the other a hydrophobic acrylic control IOL (SA60AT). Slitlamp examinations were performed at postoperative weeks 1 and 4, and at months 2, 3, and 6. The rabbits were killed humanely at 6 months. After gross examination from the Miyake-Apple view, IOLs were removed for implant cytology. All globes were then processed for histopathologic examination. Results: Uveal biocompatibility was similar between test and control IOLs up to 6 months postoperatively. Anterior capsule opacification appeared absent in the test group, and posterior capsule opacification (PCO) was significantly less in comparison with the control group throughout the study. At 6 months, central PCO was scored as 0.12 ± 0.23 with test IOLs and as 4.0 ± 0 with control IOLs (P < .0001, 2-tailed t test: paired 2-sample for means). Histopathologic examination confirmed the relative lack of capsular opacification in test eyes in comparison to controls and the absence of toxicity in any eye. Conclusions: Six weeks in the rabbit model corresponds to approximately 2 years in the human eye for PCO. In this model, the Juvene IOL maintained an open and expanded capsular bag, preventing overall capsular bag opacification while retaining excellent uveal and capsular biocompatibility.
Purpose: To determine whether a newly modified capsular tension ring (CTR) is effective at preventing toric intraocular lens (TIOL) rotation and misalignment. Setting: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Design: Experimental study. Methods: Ten human cadaver eyes were used to test the ease or difficulty of TIOL rotation in the capsular bag under 3 experimental conditions: a TIOL alone, a TIOL with a standard CTR, or a TIOL with a newly modified CTR with indentations in a sinusoidal pattern. Scores for the ease of IOL rotation were compared by using the nonparametric Friedman analysis of variance test. In addition, both anterior and posterior Miyake-Apple views were filmed to observe the rotational stability of TIOLs in the capsular bag under the 3 test conditions. Results: In the ten eyes of five patients, the rotational stability improved with a standard CTR, but further improvement was statistically observed (P < .05) with the newly modified CTR under all test conditions. This was true for both IOLs used (AcrySof and TECNIS toric IOLs), with or without ophthalmic viscosurgical device, and for either clockwise or counterclockwise rotations. Conclusions: A newly designed CTR prototype represents a new technology for improving the rotational stability of a TIOL in the capsular bag. Under all test conditions, the prototype performed significantly better than a standard CTR. The results support the use of this new CTR design to improve the accuracy and refractive success of TIOLs.
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