Influence of clusterin genetic variants on IOP elevation in pseudoexfoliation syndrome and pseudoexfoliative glaucoma in Turkish population.

PURPOSE: Pseudoexfoliation syndrome (PEX) is distinguished by the deposition of fibrillary material within the aqueous humor and, in most cases, causes pseudoexfoliative glaucoma (PEG). The pathophysiologies of PEX and PEG are not completely explained. Therefore, this study aimed to assess the potential relationship between single nucleotide polymorphisms (SNPs) in the 3' untranslated region or introns of the clusterin gene (CLU) and the susceptibility to developing PEG or PEX. METHODS: Two hundred and forty patients with PEX, 239 patients with PEG, and 240 control subjects were included. Genotyping was carried out using real-time PCR (rs2279590 C/T and rs1532278 C/T) or PCR followed by restriction endonuclease digestion (rs11136000 C/T and rs3087554 T/C). RESULTS: The minor alleles or genotypes of CLU SNPs were not significantly associated with PEX or PEG. IOP values of patients with PEX carrying the homozygote polymorphic TT genotype were significantly elevated compared with PEX cases with the CT or CC genotypes for rs2279590, rs11136000 and rs1532278 (P = .009, P = .007, P = .010, respectively). CONCLUSION: We present the first evidence that three SNPs in CLU gene (rs2279590, rs11136000 and rs1532278) might induce a rise in IOP in patients with PEX, conferring susceptibility to develop PEG.

Evaluation of oxidative stress and paraoxonase phenotypes in pseudoexfoliation syndrome and pseudoexfoliation glaucoma.

BACKGROUND: Our purpose was to determine whether total oxidant and antioxidant status, total thiol levels and activities of serum paraoxonase 1, an HDL-associated antioxidant enzyme, are related with pseudoexfoliation syndrome (PEX) and pseudoexfoliation glaucoma (PG). METHODS: Serum samples from 32 PEX, 30 PG, and 32 control subjects were collected at the Gülhane Military Medical Academy, Ankara. Basal paraoxonase (PON1), salt stimulated paraoxonase (stPON1), arylesterase (ARE), and total thiol levels were measured spectrophotometrically. Total antioxidant status (TAS) and total oxidant status (TOS) were determined on an autoanalyzer. Oxidative stress index (OSI) was calculated using the TAS and TOS values. PON1 phenotypes were calculated from the ratio of stPON1 to ARE. Continuous variables were compared by independent samples t-test and one-way ANOVA, except for age which was compared using Mann-Whitney U test. Categorical variables were compared using Fisher's exact test (PON1 phenotypes) or chi-square test (gender). RESULTS: TAS levels were significantly lower in PEX and PG patients compared to controls. TOS, OSI and total thiol levels did not differ significantly among the study groups, although there was a trend towards lower TOS and total thiol levels in patients compared to controls. PON1 activities were significantly higher in PEX patients (131.37 +/- 81.20 U/L) compared to controls (95.53 +/- 55.65 U/L; p = 0.046). The PON1 phenotype which is known to have high activity towards the substrate paraoxon, but low antioxidant activity (BB phenotype) was observed significantly more in PEX patients compared to controls. CONCLUSIONS: PON1 phenotypes and lack of antioxidants might play an important role in the development of PEX/ PG.

Biomarkers of NRF2 signalling: Current status and future challenges.

The cytoprotective transcription factor NRF2 regulates the expression of several hundred genes in mammalian cells and is a promising therapeutic target in a number of diseases associated with oxidative stress and inflammation. Hence, an ability to monitor basal and inducible NRF2 signalling is vital for mechanistic understanding in translational studies. Due to some caveats related to the direct measurement of NRF2 levels, the modulation of NRF2 activity is typically determined by measuring changes in the expression of one or more of its target genes and/or the associated protein products. However, there is a lack of consensus regarding the most relevant set of these genes/proteins that best represents NRF2 activity across cell types and species. We present the findings of a comprehensive literature search that according to stringent criteria identifies GCLC, GCLM, HMOX1, NQO1, SRXN1 and TXNRD1 as a robust panel of markers that are directly regulated by NRF2 in multiple cell and tissue types. We assess the relevance of these markers in clinically accessible biofluids and highlight future challenges in the development and use of NRF2 biomarkers in humans.

Theranostic potential of graphene quantum dots for multiple sclerosis.

Nanomedicine offers great promise to solve healthcare problems using nanotechnology. Theranostics provide imaging/diagnosis and therapy simultaneously. Novel agents that target both the neuroinflammation and neurodegeneration component of multiple sclerosis (MS) are required. Progress has been achieved in developing smart, surface decorated nanoparticles that effectively transport the therapeutic drug into the central nervous system (CNS). Graphene quantum dots (GQDs) can be traced in vivo by fluorescence imaging due to their unique optical properties. They can also traverse the blood-brain barrier (BBB) and deliver drugs into the CNS. Moreover, GQDs have low cytotoxicity and higher biocompatibility. Therefore, GQDs can be utilized to design novel multifunctional nanocarrier theranostic tools for MS.

Analysis of paraoxonase 1 (PON1) genetic polymorphisms and activities as risk factors for ischemic stroke in Turkish population.

BACKGROUND: Paraoxonase1 (PON1) is protective against the development of atherosclerosis, a risk factor for ischemic stroke. PON1 gene has one promoter region (-107T/C) and two coding region (192Q/R and 55L/M) polymorphisms that affect the levels and catalytic efficiency of the enzyme, respectively. In this study, we aimed to determine the importance of -107T/C, 192Q/R and 55L/M polymorphisms of PON1 gene and three PON1 activities (diazoxonase, paraoxonase, arylesterase) as risk factors for ischemic stroke. METHODS: Study population was comprised of 172 unrelated adult Caucasian patients with acute hemispheric ischemic stroke and 105 symptom-free controls. Genotypes were attained by PCR followed by restriction enzyme digestion and phenotypes were determined by spectrophotometric assays. RESULTS: This is the first study analyzing diazoxonase activity as a risk factor for ischemic stroke. Nevertheless, diazoxonase, paraoxonase and arylesterase activities were almost the same in stroke patients and controls. The -107TT genotype was associated with a 1.97 times increased risk for stroke in elderly (age > 59). Individuals with this genotype were found to have the lowest PON1 enzyme activities among the -107T/C genotypes. Triple combined haplotype QRLMTC was found to be 6.94- and 10.4-times protective against ischemic stroke in the overall and the elderly population, respectively. 55LL genotype was associated with a 1.78-fold increase in the risk of ischemic stroke. CONCLUSION: PON1 genotypes, but not activities, are related with the risk of stroke.