A smart contact lens can be used as an excellent interface between the human body and an electronic device for wearable healthcare applications. Despite wide investigations of smart contact lenses for diagnostic applications, there has been no report on electrically controlled drug delivery in combination with real-time biometric analysis. Here, we developed smart contact lenses for both continuous glucose monitoring and treatment of diabetic retinopathy. The smart contact lens device, built on a biocompatible polymer, contains ultrathin, flexible electrical circuits and a microcontroller chip for real-time electrochemical biosensing, on-demand controlled drug delivery, wireless power management, and data communication. In diabetic rabbit models, we could measure tear glucose levels to be validated by the conventional invasive blood glucose tests and trigger drugs to be released from reservoirs for treating diabetic retinopathy. Together, we successfully demonstrated the feasibility of smart contact lenses for noninvasive and continuous diabetic diagnosis and diabetic retinopathy therapy.
Fifteen molecules were elevated in the tears of patients with DED; four molecules were decreased. Although the levels of sIL-6R, sIL-6R, and sgp130 may be potential indicators of the homeostatic process, an increase in the levels of IL-6 and IL-1 β are the earliest observable changes in patients with DED. Further study on the biomarkers in the pathogenesis of DED and treatment target modalities would be needed.
Purpose To investigate the possibility of collagen type VIII a2 (COL8A2) as a potential susceptibility gene for Korean patients with Fuchs' corneal dystrophy (FECD), we performed mutation screening of the COL8A2 gene. Methods A total of 25 FECD patients were screened, including 15 patients from six pedigrees with early onset FECD and an additional 10 unrelated patients, all of Korean ancestry. Seventy-three control individuals without corneal disease were selected from the general population. PCRFSSCP and direct sequencing were used to screen genetic variations in COL8A2. The pathogenic impact of these sequence variants was evaluated through the SIFT and PolyPhen algorithms.Results We have identified a novel heterozygous mutation, Q455V, in exon 2 of COL8A2. All patients of Korean pedigrees with FECD had the Q455V mutation, and two out of nine unrelated cases also had this mutation. But it was not present in unaffected individuals from these pedigrees or from control groups. Two heterozygous missense mutations, R155Q and T502M, were also observed, but, they showed no significant difference between FECD patients and controls. The allele frequencies of A35A and G495G, which were synonymous substitutions, were significantly associated with FECD. Both Q455V and T502M were predicted as deleterious mutations by computational methods using PolyPhen and SIFT. Conclusions Our data constitute the first report of a heterozygous Q455V mutation of the COL8A2 gene in Korean patients with FECD. Q455V may be the causative defect in the development and progression of Korean FECD patients.
Based on the findings, OOK was a relatively safe modality. However, given the potential changes in the meibomian gland and tear film stability, special attention must be paid to children with baseline meibomian gland distortions or a history of allergic conditions.
Smart contact lenses for continuous glucose monitoring (CGM) have great potential for huge clinical impact. To date, their development has been limited by challenges in accurate detection of glucose without hysteresis for tear glucose monitoring to track the blood glucose levels. Here, long‐term robust CGM in diabetic rabbits is demonstrated by using bimetallic nanocatalysts immobilized in nanoporous hydrogels in smart contact lenses. After redox reaction of glucose oxidase, the nanocatalysts facilitate rapid decomposition of hydrogen peroxide and nanoparticle‐mediated charge transfer with drastically improved diffusion via rapid swelling of nanoporous hydrogels. The ocular glucose sensors result in high sensitivity, fast response time, low detection limit, low hysteresis, and rapid sensor warming‐up time. In diabetic rabbits, smart contact lens can detect tear glucose levels consistent with blood glucose levels measured by a glucometer and a CGM device, reflecting rapid concentration changes without hysteresis. The CGM in a human demonstrates the feasibility of smart contact lenses for further clinical applications.
A cholesterol-hyaluronate (C-HA) micelle embedded contact lens was developed for efficient hydrophobic drug loading and long-term controlled drug delivery.
We assayed for germline single nucleotide polymorphisms (SNPs) in the TNFB and TNFA genes in patients with breast cancer. SNPs were observed in the first intron of TNFB (G/A) and at -1031 (T/C), -863 (C/A), -857 (C/T) and -308 (G/A) in the promoter region of TNFA from peripheral leucocytes in 95 breast cancer patients and 190 healthy subjects as controls. The TNFB*G/TNFB*G homozygote (23.2% vs. 5.8%, P= 0.001) was predominant in patients, while the TNFB*A/TNFB*A homozygote was less frequent in patients (34.7% vs. 46.3%, P = 0.041) than in the control subjects. Breast cancer was not associated with SNPs in the TNFA promoters. Although the TNFB SNP failed to associate with any clinicopathological parameter of breast cancer, a substantial difference in pathology among tumour stages for the -857 SNP in TNFA was detected. These results indicate that TNFB has both tumorigenic and antitumorigenic capabilities depending on the genotype: the TNFB SNP TNFB*G/TNFB*G genotype gave an increased risk for breast cancer and that of TNFB*A/TNFB*A gave resistance to breast cancer (OR = 5.3395%; CI: 2.33-12.19). The results suggest that the TNFB*G allele plays some role in the tumorigenesis or activation of dormant tumour cells, but the TNFB*A allele induces some function(s) leading to the inhibition of tumorigenesis.
Keratoconus is a bilateral ectatic disorder characterized by the central thinning of corneal tissue leading to visual impairment. To investigate the possibility of visual system homeobox 1 (VSXI) as a candidate susceptibility gene for Korean patients with keratoconus, we performed a mutation screening of the VSXI gene in 249 unrelated patients with keratoconus and 208 control subjects without the ocular disorder. We found two heterozygous novel missense mutations in exon 2: N151S and G160V. The G160V mutation was identified in 13 keratoconus patients (5.3%), and the N151S mutation was found in only one keratoconus patient (0.4%). We also detected three synonymous polymorphisms and four intragenic polymorphisms. The IVS1-11*a allele was associated with a significantly increased risk of keratoconus in Korean patients [3.6 vs. 0.5%, p = 0.001, odds ratio (OR) = 7.76, 95% confidence interval (CI) 1.989-30.241). Other polymorphisms did not show an association with keratoconus risk. Our data is the first reported VSX1 mutation screening in Korean keratoconus patients. We detected two novel missense mutations and one intragenic polymorphism in the VSX1 gene, which show a strong statistical association with unrelated keratoconus patients. Consequently, our study suggests that VSX1 gene variants seem to be significant genetic variants for keratoconus predisposition in unrelated Korean patients.
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