APOE ε2-Carriers Are Associated with an Increased Risk of Primary Angle-Closure Glaucoma in Patients of Saudi Origin.

This study investigated the association between apolipoprotein E (APOE) gene polymorphisms (rs429358 and rs7412) and primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG) in a Saudi cohort. Genotyping of 437 DNA samples (251 controls, 92 PACG, 94 PXG) was conducted using PCR-based Sanger sequencing. The results showed no significant differences in the allele and genotype frequencies of rs429358 and rs7412 between the PACG/PXG cases and controls. Haplotype analysis revealed ε3 as predominant, followed by ε4 and ε2 alleles, with no significant variance in PACG/PXG. However, APOE genotype analysis indicated a significant association between ε2-carriers and PACG (odds ratio = 4.82, 95% CI 1.52-15.26, p = 0.007), whereas no notable association was observed with PXG. Logistic regression confirmed ε2-carriers as a significant predictor for PACG (p = 0.008), while age emerged as significant for PXG (p < 0.001). These findings suggest a potential role of ε2-carriers in PACG risk within the Saudi cohort. Further validation and larger-scale investigations are essential to elucidate the precise role of APOE in PACG pathogenesis and progression.

Common Variants rs429358 and rs7412 in APOE Gene Are Not Associated with POAG in a Saudi Cohort.

Adult-onset glaucoma, an age-related neurodegenerative disease, is very prevalent among the elderly Arabs of Saudi origin. This study investigated the association between apolipoprotein E (APOE) gene variants (rs429358 and rs7412) and primary open-angle glaucoma (POAG) in Arabs of Saudi origin. A case-control genetic association study involving 179 POAG patients and 251 controls utilized Sanger sequencing to genotype APOE gene variants. The allele frequencies and genotype distributions for rs429358 and rs7412 did not show significant associations with POAG. The haplotype analysis revealed apoε3 (87.6% and 87.4%) as the most prevalent, followed by ε4 (2.8% and 3.6%) and ε2 (9.6% and 8.9%) in the controls and POAG patients, respectively. Although the ε2/ε3 genotype and ε2-carriers displayed a more than two-fold increased risk, statistical significance was not reached. Notably, these polymorphisms did not affect clinical markers, such as intraocular pressure and cup/disc ratio. The logistic regression analysis demonstrated no significant influence of age, sex, rs429358, or rs7412 polymorphisms on POAG. In conclusion, within the Saudi cohort, APOE variants (rs429358 and rs7412) do not appear to be associated with POAG and are not substantial risk factors for its development. However, additional population-based studies are required to validate these findings.

Association between Polymorphism rs61876744 in PNPLA2 Gene and Keratoconus in a Saudi Cohort.

The genetic etiology of Keratoconus (KC) in Middle Eastern Arabs of Saudi origin is still unclear. A recent genome-wide study identified two significant loci in the region of PNPLA2 (rs61876744) and CSNK1E (rs138380) for KC that may be associated with KC in the Saudi population. In addition, polymorphisms in the apolipoprotein E (APOE) gene, namely, rs429358 and rs7412, responsible for APOE allelic variants ε2, ε3, and ε4, may influence KC via oxidative stress mechanism(s). Thus, we investigated the possible association of polymorphisms rs61876744, rs138380, rs429358, rs7412, and APOE genotypes in KC patients of the Saudi population. This study included 98 KC cases and 167 controls. Polymorphisms rs6187644 and rs138380 were genotyped using TaqMan assays, and rs429358 and rs7412 were genotyped via Sanger sequencing. Although the allele frequency of rs61876744(T) in PNPLA2 was a protective effect against KC (odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.44-0.93), the p-value (p = 0.020) was not significant for multiple testing correction (p = 0.05/4 = 0.015). However, rs6187644 genotype showed a modestly significant protective effect in the dominant model (OR = 0.53, 95% CI = 0.32-0.88, p = 0.013). Polymorphisms rs138380, rs429358, and rs7412 showed no significant allelic or genotype association with KC. However, the ε2-carriers (ε2/ε2 and ε2/ε3 genotypes) exhibited a greater than 5-fold increased risk of KC, albeit non-significantly (p = 0.055). Regression analysis showed no significant effect of age, gender, and the four polymorphisms on KC. Our results suggest that polymorphism rs6187644 in PNPLA2 might be associated with KC in the Middle Eastern Arabs of Saudi origin but warrant a large-scale association analysis at this locus.

The 3' UTR polymorphisms rs3742330 in DICER1 and rs10719 in DROSHA genes are not associated with primary open-angle and angle-closure glaucoma: As case-control study.

AIM: In a retrospective and exploratory case-control study, we examined the genetic association of two common polymorphisms in the 3' untranslated region (UTR) of DICER1 (rs3742330) and DROSHA (rs10719) genes in primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), and its related clinical phenotypes in a Saudi cohort. METHODS: DNA genotyping was performed using TaqMan real-time PCR assays in 500 participants, including 152 POAG, 102 PACG, and 246 non-glaucomatous controls. Statistical analyses were performed to examine the association(s). RESULTS: Allele and genotype frequency of rs3742330 and rs10719 did not vary significantly in POAG and PACG compared to controls. No significant deviation was observed from Hardy-Weinberg Equilibrium (p > 0.05). Gender stratification revealed no significant allelic/genotype association with glaucoma types. Also, these polymorphisms showed no significant genotype effect on clinical markers such as intraocular pressure, cup/disc ratio, and the number of antiglaucoma medications. Logistic regression showed no effect of age, sex, rs3742330, and rs10719 genotypes on the risk of disease outcome. We also examined a combined allelic effect of rs3742330 (A>G) and rs10719 (A>G). However, none of the allelic combinations significantly affected POAG and PACG. CONCLUSIONS: The 3' UTR polymorphisms rs3742330 and rs10719 of DICER1 and DROSHA genes are not associated with POAG and PACG or its related glaucoma indices in this Middle-Eastern cohort of Saudi Arab ethnicity. However, there is a need to validate the results on a broader population and other ethnicities.

Lack of Association of Polymorphism Located Upstream of ABCA1 (rs2472493), in FNDC3B (rs7636836), and Near ANKRD55-MAP3K1 Genes (rs61275591) in Primary Open-Angle Glaucoma Patients of Saudi Origin.

Polymorphisms rs2472493 near ABCA1, rs7636836 in FNDC3B, and rs61275591 near the ANKRD55-MAP3K1 genes were previously reported to exhibit genome-wide significance in primary open-angle glaucoma (POAG). Since these polymorphisms have not been investigated in the Arab population of Saudi Arabia, we examined their association with POAG in a Saudi cohort. Genotyping was performed in 152 POAG cases and 246 controls using Taqman real-time assays and their associations with POAG and clinical markers, such as intraocular pressure, cup/disc ratio, and the number of antiglaucoma medications, were tested by statistical methods. There was no association observed between POAG and the minor allele frequencies of rs2472493[G], rs7636836[T], or rs61275591[A]. None of the genetic models such as co-dominant, dominant, recessive, over-dominant, and log-additive demonstrated any genotype link. The Rs2472493 genotype showed a modest association (p = 0.044) with the number of antiglaucoma medications in the POAG group, but no significant genotype effect on post hoc analysis. In addition, a G-T allelic haplotype of rs2472493 (ABCA1) and rs7636836 (FNDC3B) did show an over two-fold increased risk of POAG (odds ratio = 2.18), albeit non-significantly (p = 0.092). Similarly, no other allelic haplotype of the three variants showed any significant association with POAG. Our study did not replicate the genetic association of rs2472493 (ABCA1), rs763683 (FNDC3B), and rs61275591 (ANKRD55-MAP3K1) in POAG and related clinical phenotypes, suggesting that these polymorphisms are not associated with POAG in a Saudi cohort of Arab ethnicity. However, large population-based multicenter studies are needed to validate these results.

Evaluation of ABCA1 and FNDC3B Gene Polymorphisms Associated With Pseudoexfoliation Glaucoma and Primary Angle-Closure Glaucoma in a Saudi Cohort.

Objective: It is plausible that common disease mechanisms exist in glaucoma pathophysiology. Accordingly, we investigated the genetic association of two previously reported primary open-angle glaucoma (POAG)-related gene polymorphisms, rs2472493 (A > G) in ABCA1 and rs7636836 (C > T) in FNDC3B, in primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG). Methods: TaqMan genotyping was performed in a total of 442 subjects consisting of 246 healthy controls, 102 PACG patients, and 94 PXG patients. Statistical evaluations were performed to detect allelic and genotype association of the variants with the disease and clinical variables such as intraocular pressure (IOP) and cup/disc ratio. Results: Overall, there was no allelic or genotype association of these variants in PACG and PXG. However, rs7636836[T] allele significantly increased the risk of PXG among men (p = 0.029, odds ratio [OR] = 2.69, 95% confidence interval = 1.11-6.51). Similarly, rs2472493 and rs7636836 genotypes also showed significant association with PXG among men in over-dominant model (p = 0.031, OR = 1.98, 95% CI = 1.06-3.71) and co-dominant model (p = 0.029, OR = 2.69, 95% CI = 1.11-6.51), respectively. However, none survived Bonferroni's correction. Besides, the synergic presence of rs2472493[G] and rs7636836[T] alleles (G-T) was found to significantly increase the risk of PACG (p = 0.026, OR = 2.85, 95% CI = 1.09-7.46). No significant genotype influence was observed on IOP and cup/disc ratio. Conclusion: Our results suggest that the polymorphisms rs2472493 in ABCA1 and rs7636836 in FNDC3B genes may be associated with PXG among men, and a G-T allelic combination may confer an increased risk of PACG in the middle-eastern Saudi cohort. Further research in a larger population-based sample is needed to validate these findings.

Polymorphism rs3742330 in microRNA Biogenesis Gene DICER1 Is Associated with Pseudoexfoliation Glaucoma in Saudi Cohort.

We investigated the association between DICER1 (rs3742330) and DROSHA (rs10719) polymorphisms and pseudoexfoliation glaucoma (PXG) and related clinical phenotypes in a Saudi cohort. In a retrospective case-control study, TaqMan real-time, PCR-based genotyping was performed in 340 participants with 246 controls and 94 PXG cases. The minor (G) allele frequency of rs3742330 in PXG (0.03) was significantly different from that in the controls (0.08) and protective against PXG (odds ratio (OR) = 0.38, 95% confidence interval (CI) = 0.16-0.92), p = 0.017). Similarly, the rs3742330 genotypes showed a significant protective association with PXG in dominant (p = 0.019, OR = 0.38, 95% CI = 0.15-0.92), over-dominant (p = 0.024, OR = 0.39, 95% CI = 0.16-0.95), and log-additive models (p = 0.017, OR = 0.38, 95% CI = 0.16-0.92). However, none remained significant after an adjustment for age, sex, and multiple testing. Rs10719 in DROSHA did not show any significant allelic or genotype association with PXG. However, a protective effect of the GA haplotype in DICER1 and DROSHA and PXG (p = 0.034) was observed. Both polymorphisms showed no significant effect on intraocular pressure and the cup-disk ratio. In conclusion, we report a significant genetic association between variant rs3742330 in DICER1, a gene involved in miRNA biogenesis, and PXG. Further investigation in a larger group of patients of different ethnicities and functional studies are warranted to replicate and validate its potential role in PXG.

Association analysis of variants rs35934224 in TXNRD2 and rs6478746 in LMX1B in primary angle-closure and pseudoexfoliation glaucoma.

OBJECTIVE: Previous genome-wide studies have demonstrated significant pathogenic association between variants rs35934224 within TXNRD2 and rs6478746 near LMX1B in primary open-angle glaucoma. We investigated the association between these variants in primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG) patients of Saudi origin. METHODS: In a case-control study, DNA samples from 249 controls (135 men and 114 women), 100 PACG cases (44 men and 56 women), and 95 PXG cases (61 men and 34 women) were genotyped by TaqMan® based real-time PCR. Statistical tests were performed to evaluate genetic association with glaucoma types and related clinical indices. RESULTS: The allele frequencies of rs35934224 and rs6478746 did not show significant variation in PACG and PXG than controls, except that the rs35934224[T] allele was found to be significantly low among PXG women (0.10) as compared to controls (0.21) (odds ratio = 0.38, 95% confidence interval = 0.16-0.94, p = 0.024). Rs35934224 genotypes showed a nominal-to-borderline protective association with PACG and PXG among women in different genetic models. However, except for the over-dominant model in PACG (p = 0.0095), none of the effects survived Bonferroni's correction (p < 0.01). Rs6478746 showed no significant genotype or allelic association with PACG and PXG. Regression analysis showed no influence on disease outcome, and neither showed any correlation with intraocular pressure and cup/disk ratio in both PACG and PXG. CONCLUSIONS: Variants rs35934224 in TXNRD2 and rs6478746 near LMX1B are not associated with PACG and PXG in the Saudi cohort, but rs35934224 may confer modest protection among women. Further population-based studies are needed to validate these results.

Bilateral Multiple Ciliary Body Cysts with Angle-Closure Glaucoma in an 18-Year-Old Patient.

We present the rare case of an 18-year-old medically free male who had a history of decrease in vision in the left eye (LE) in the last 4 years. On examination, best-corrected visual acuity was 20/20 in the right eye (RE) and counting fingers 3 feet in the LE. Intraocular pressure was 34 and 40 mmHg in RE and LE, respectively. Fundus examination showed cupping of 0.7 on the RE and 0.9 on the LE. Gonioscopy revealed bilateral angle closure with a double-hump sign. Ultrasound biomicroscopy showed multiple ciliary body cysts replacing ciliary body sulcus space bilaterally.

Lack of Association Between Polymorphisms in TXNRD2 and LMX1B and Primary Open-Angle Glaucoma in a Saudi Cohort.

Objective: Recent studies have demonstrated an association of single nucleotide polymorphisms (SNPs) rs35934224 in TXNRD2 and rs6478746 near LMX1B genes in primary open-angle glaucoma (POAG) among Europeans. We performed a retrospective, case-control study to investigate the association between the rs35934224 (TXNRD2) and rs6478746 (LMX1B) and POAG in a middle-eastern population from Saudi Arabia. Methods: DNA from 399 participants consisting of 150 POAG cases (83 males and 67 females) and 249 controls (135 males and 114 females) were genotyped using TaqMan® real-time PCR. Statistical tests were performed to evaluate genetic association with POAG and related clinical indices. Results: The minor allele frequency (MAF) of rs35934224[T] was 0.19 and 0.20 in POAG and controls, respectively. The difference was non-significant (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 0.75-1.55, p = 0.663). Likewise, rs6478746[G] MAF was 0.12 in both cases and controls with no statistical significance (OR = 1.02, 95% CI = 0.67-1.56, p = 0.910). Genotype analysis showed no association with POAG for both the SNPs in combined and gender-stratified groups. Regression analysis showed no significant effect of risk factors such as age, sex, rs35934224, and rs6478746 genotypes on POAG outcome. Furthermore, both the SNPs showed no significant genotype effect on clinical indices such as intraocular pressure (IOP) and cup/disc ratio in POAG patients. Conclusions: Rs35934224 in TXNRD2 and rs6478746 near LMX1B genes are not associated with POAG or related clinical indices such as IOP and cup/disc ratio in a Saudi cohort. Since the study is limited by sample size further investigations are needed to confirm these results in a larger cohort.

Association of rs12997 variant in the ACVR1 gene: a member of bone morphogenic protein signaling pathway with primary open-angle glaucoma in a Saudi cohort.

We investigated the association between variants rs12997 in activin A receptor type I (ACVR1) and rs1043784 in BMP6 located in the 3' untranslated region, and primary open-angle glaucoma (POAG). The retrospective case-control study used TaqMan real-time PCR assay to genotype 400 subjects, including 150 patients with POAG and 250 controls. The minor 'G' allele of rs12997 in ACVR1 showed significant association with POAG (p=0.027, OR=1.39, 95% CI=1.03 to 1.87). Likewise, rs12997 genotypes showed moderate association with POAG in recessive (p=0.048, OR=1.80, 95% CI=1.01 to 3.20) and log-additive models (p=0.030, OR=1.39, 95% CI=1.03 to 1.87), but did not survive Bonferroni correction. Rs1043784 in BMP6 showed no associations. Furthermore, rs12997 G/G genotype significantly (p=0.033) increased the risk of POAG (twofolds) independent of age, sex and rs1043784 genotypes in regression analysis. However, clinical variables such as intraocular pressure and cup/disc ratio showed no association with both the polymorphisms. To conclude, the study shows a modest association between rs12997 in the ACVR1 gene, a member of the bone morphogenic protein signaling pathway and POAG. However, the results need further replication in large population-based cohorts and different ethnicities to validate its role as an important genetic biomarker.

Acute hydrops as an atypical presentation of primary congenital glaucoma.

Primary congenital glaucoma (PCG) is a disease of childhood characterized by elevated intraocular pressure (IOP) that causes stretching of the eye's outer coats, namely sclera and cornea. This results in the elongation of the eyeball and expansion of the horizontal corneal diameter giving the appearance of a buphthalmos eye. Aggressive disease with high IOP readings causes excessive mechanical stretching that may be poorly tolerated by the corneal Descemet's membrane, leading to large breaks in it with subsequent corneal edema due to sudden influx of the aqueous humor into the exposed stroma, resulting in acute corneal hydrops. While acute hydrops is a potential sequel of PCG, it is considered one of its rare presentations. We present two cases who presented to our hospital with acute hydrops secondary to PCG. Both patients were managed surgically where the first patient underwent combined trabeculotomy-trabeculectomy with mitomycin C, while the second patient underwent deep sclerectomy with mitomycin C. The surgical procedures effectively controlled the IOP and aided in clearing corneal edema in both patients. Early diagnosis and timely surgical intervention are of paramount importance to improve visual outcomes, enhance ocular maturation, and prevent potential irreversible vision loss, especially in this young-age group of patients that are prone to amblyopia.

Association analysis of polymorphisms rs12997 in ACVR1 and rs1043784 in BMP6 genes involved in bone morphogenic protein signaling pathway in primary angle-closure and pseudoexfoliation glaucoma patients of Saudi origin.

BACKGROUND: Glaucoma is a polygenic neurodegenerative disease and the second most common cause of blindness in Saudi Arabia. To test the hypothesis that genetic variants in the genes involved in the bone morphogenic protein (BMP) signaling pathway may be associated with glaucoma, we investigated the association between 3' untranslated region variants, rs12997 in ACVR1 and rs1043784 in BMP6, and primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG). METHODS: In a case-control study, TaqMan® real-time PCR-based genotyping was done in 444 subjects consisting of 250 controls, 101 PACG and 95 PXG cases, and tested for genetic association with glaucoma-types and other clinical phenotypes. RESULTS: Rs12997[G] allele in ACVR1 exhibited significant 2-fold increased risk of PACG (p = 0.005) in women but not in men. Similarly, genotype analysis also showed that subjects carrying rs12997[G/G] genotype were at > 2-fold risk of PACG that remained significant after adjustment for age, sex, and Bonferroni correction in the recessive model. Furthermore, this effect was also significant in women only. In PXG, the rs12997[G/G] genotype showed a significant trend towards increased risk of the disease (OR = 2.04, 95% CI = 0.99-4.18, p = 0.049) but did not survive the Bonferroni correction. Regression analysis showed that rs12997[G/G] genotype was a significant predictor of PACG independent of age, sex, and rs1043784 genotypes. Likewise, age and rs12997[G/G] genotype showed significant effect on PXG outcome. The rs12997[A/G] genotype showed significant association with cup/disc ratio as compared to wild-type (p = 0.005) in PXG. Genotype and allele frequencies of rs1043784 in BMP6 did not show any significant association either with PACG or PXG. CONCLUSIONS: Our results suggest that the polymorphism rs12997 in the ACVR1 gene involved in the BMP signaling pathway is significantly associated with PACG and PXG in a Saudi cohort. This is the first study to associate this variant/gene with PACG and PXG. However, further studies would be needed to replicate these findings in a large population-based cohort.

Elevated Plasma Level of 8-Hydroxy-2'-deoxyguanosine Is Associated with Primary Open-Angle Glaucoma.

PURPOSE: To determine the association between plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, a marker for oxidative DNA damage, and patients with primary open-angle glaucoma (POAG) or its clinical phenotypes. Furthermore, we also examined the utility of plasma 8-OHdG as a potential biomarker in POAG. MATERIALS AND METHODS: In a retrospective case-control study, plasma samples were obtained from 50 POAG cases and 45 glaucoma-free controls matched for age, sex, and ethnicity. 8-OHdG levels were measured in duplicate using an enzyme-linked immunosorbent assay (ELISA) on an automated ELISA analyzer. RESULTS: There was no significant difference in age, sex, and systemic disease distribution between POAG cases and controls. Both mean and median 8-OHdG levels were significantly elevated in POAG cases and male subjects. The area under the receiver operating characteristic (ROC) curve value for plasma 8-OHdG was 0.653 (95% confidence interval = 0.54-0.76, p = 0.010). The cutoff values based on quartile distribution and ROC curve analysis showed that elevated plasma 8-OHdG significantly increased the risk of POAG by more than 4-folds. Plasma 8-OHdG had a sensitivity of 78% and specificity of 53%. In logistic regression analysis, 8-OHdG showed a significant effect on POAG outcome (p = 0.016) independent of age, sex, smoking, and systemic diseases. However, no significant correlation was observed between 8-OHdG and specific clinical markers of glaucoma such as intraocular pressure (p = 0.699), cup/disc ratio (p = 0.213), and the number of antiglaucoma medications (p = 0.603). CONCLUSION: The study shows that there is a significant association between elevated plasma 8-OHdG and POAG, supporting the role of systemic oxidative stress-induced DNA damage in POAG pathogenesis. However, with a high rate of false-positivity, plasma 8-OHdG may lack the ability to serve as a potential biomarker in POAG. Further studies in a much larger cohort are needed to confirm these findings.

Association of endothelial nitric oxide synthase (NOS3) gene polymorphisms with primary open-angle glaucoma in a Saudi cohort.

AIM: To investigate the association of endothelial nitric oxide synthase (NOS3) gene polymorphisms in patients with primary open-angle glaucoma (POAG) of Saudi origin. METHODS: This case-control study included 173 patients with POAG (94 men and 79 women) and 171 controls (98 men and 73 women). Genotyping of rs2070744 (T-786C) and rs1799983 (G894T) variants of the NOS3 gene was performed using TaqMan® assay. RESULTS: Rs1799983 genotypes showed a significant association with POAG but did not survive Bonferroni correction (pcorrection = 0.01). The minor 'T' allele was significantly associated with the risk of POAG among men (p = 0.025, odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.07-2.94). Likewise, the genotypes were significantly associated with POAG among men in dominant (p = 0.030, OR = 1.92, 95% CI = 1.06-3.48) and log-additive models (p = 0.022, OR = 1.82, 95% CI = 1.08-3.07), and after adjustment for age and smoking. Genotype and allele frequencies of rs2070744 were not significantly different between POAG cases and controls, and after sex stratification. CG haplotype was significantly protective (p = 0.011, OR = 0.52, 95% CI = 0.32-0.87) and CT haplotype conferred significantly increased risk of POAG (p = 0.016, OR = 2.60, 95% CI = 1.16-5.82) among men. Rs1799983 showed trend (p = 0.054) towards risk of POAG independent of age, gender, smoking, and rs2070744 polymorphism in logistic regression analysis. Both the polymorphisms showed no association with POAG phenotypes such as intraocular pressure and cup/disc ratio. CONCLUSION: Our results suggest that the polymorphism rs1799983 and the haplotypes of rs20707440 and rs1799983 in the NOS3 gene may significantly modulate the risk of POAG in Saudi's, particularly among men. Further larger studies are needed to confirm these findings.

Local Cytokine Expression Profiling in Patients with Specific Autoimmune Uveitic Entities.

Purpose: To evaluate expression of cytokines GM-CSF, IL-11, IL-12p40, IL-12p70, IL-27p28, IL-35, APRIL, BAFF, TWEAK, and LIGHT in uveitis.Methods: Aqueous humor samples from patients with active uveitis associated with Behçet's disease (BD), sarcoidosis, HLA-B27-related inflammation, and Vogt-Koyanagi-Harada (VKH) disease and control patients were assayed with a multiplex assay.Results: Comparing all patients to controls, GM-CSF, IL-11, IL-12p40, APRIL, and BAFF were significantly increased, whereas LIGHT was significantly decreased. IL-11 and BAFF were the most strongly upregulated, being elevated 19.7-fold and 14.1-fold, respectively, compared with controls. IL-11 was significantly highest in HLA-B27 uveitis. GM-CSF, IL-11, and IL-12p40 were significantly higher in nongranulomatous uveitis (BD and HLA-B27) than in granulomatous uveitis (sarcoidosis and VKH), whereas APRIL and TWEAK were significantly higher in granulomatous uveitis.Conclusions: IL-11-driven immune responses might be more potent in nongranulomatous uveitis, particularly in HLA-B27 uveitis. BAFF and APRIL might contribute to B cell-driven autoimmune response in uveitis.

Soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities: sCD30 is a biomarker of granulomatous uveitis.

PURPOSE: Soluble cytokine receptors are potential biomarkers for immune activation and have a promising potential as immunotherapeutic agents. We investigated the levels of soluble cytokine receptors in aqueous humour (AH) samples from patients with specific autoimmune uveitic entities. METHODS: Patients with active uveitis associated with Behçet's disease (BD) (n = 13), sarcoidosis (n = 8), HLA-B27-related inflammation (n = 12), Vogt-Koyanagi-Harada (VKH) disease (n = 12) and control subjects (n = 9) were included. AH samples were analyzed with the use of multiplex assays for the proinflammatory cytokine tumour necrosis factor (TNF)-α and the soluble cytokine receptors sCD30, sCD163, sgp130, sIL-6 receptor-α (sIL-6R), sTNFRI and sTNFRII. RESULTS: TNF-α and soluble cytokine receptor AH levels were significantly higher in uveitis patients (n = 45) compared with controls (n = 9). When nongranulomatous uveitis (BD and HLA-B27-associated uveitis) was compared with granulomatous uveitis (sarcoidosis and VKH disease), the levels of sCD30 and sTNFRI/TNF-α and sTNFRII/TNF-α ratios were significantly enhanced in granulomatous uveitis. Finally, when comparing the profile in the specific uveitis entities, sCD30 levels were highest in patients with VKH disease. sgp130, sCD163, sIL-6R, sTNFRI and sTNFRII did not differ significantly between the four different clinical uveitic subgroups. CONCLUSIONS: Soluble cytokine receptors are significantly upregulated in autoimmune uveitis. CD30+ T cells might contribute to the inflammatory process in granulomatous uveitis, particularly in VKH disease. Granulomatous uveitis is also characterized by significantly higher sTNFRs/TNF-α ratios than nongranulomatous uveitis.

Polymorphisms rs693421 and rs2499601 at locus 1q43 and their haplotypes are not associated with primary open-angle glaucoma: a case-control study.

OBJECTIVE: The genetic spectrum of primary open-angle glaucoma (POAG) in middle-eastern Saudi's is still elusive. To this end, we investigated an association between rs693421, rs2499601 and their haplotypes at chromosome 1q43 locus with POAG and its related clinical phenotypes. Genotyping was performed with TaqMan® assays. Haplotypes and their interaction analysis were carried out by SHEsis and SNPStats online tools. RESULTS: The minor "T" allele frequency of rs693421 was 0.48 in controls and 0.52 in cases (odds ratio (OR) = 1.15, 95% confidence interval (CI) 0.85-1.54, p = 0.368). Similarly, for rs2499601, the minor "C" allele frequency was 0.49 in controls as compared to 0.53 in cases (OR = 1.19, 95% CI 0.89-1.60, p = 0.236). Besides, genotype distribution for both these polymorphisms was also not significant in additive, dominant and recessive models. rs693421 and rs2499601, showed significant linkage disequilibrium (D' statistics = 0.69, p < 0.001) but haplotype association was non-significant (p = 0.698). The significance did not vary after adjustment to age and sex. No significant genotype association was observed with intraocular pressure, cup/disc ratio and number of anti-glaucoma medication in POAG group. Furthermore, age, sex and genotypes did not contribute any significant risk of POAG in regression analysis. We report no association between rs693421, rs2499601 and their haplotypes with POAG and related phenotypes.

Increased Plasma Levels of 8-Hydroxy-2'-deoxyguanosine (8-OHdG) in Patients with Pseudoexfoliation Glaucoma.

PURPOSE: To investigate systemic oxidative stress-induced DNA damage in patients with pseudoexfoliation glaucoma (PXG), we estimated plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a marker for oxidative DNA damage in comparison to controls. In addition, we also examined a combined effect of lysyl oxidase-like 1 (LOXL1) polymorphism status and 8-OHdG levels on PXG risk. MATERIALS AND METHODS: A retrospective case-control study was performed to estimate plasma levels of 8-OHdG in 41 PXG patients and 45 nonglaucomatous controls using the enzyme-linked immunosorbent assay (ELISA). The assay was performed in duplicate on an automated ELISA analyzer. Two common polymorphisms (rs1048661 and rs3835942) in LOXL1 gene were genotyped by Sanger sequencing. RESULTS: The mean and median levels of 8-OHdG were significantly increased in the PXG cases (p=0.032) and male subjects (p=0.041). Subjects with levels greater than the third quartile (75% percentile) exhibited a significant increased risk of PXG (odds ratio = 4.06, 95% confidence interval (CI = 1.11-14.80, p=0.029)). Within- and between-group comparisons showed that the mean levels were higher in individuals carrying the LOXL1 risk variant (G/G), but not statistically significant. In logistic regression analysis, both 8-OHdG (p=0.044) and rs3835942 (p=0.012) showed a statistically significant effect on the PXG outcome. However, the effect was lost when age, sex, and rs1048661 were included. A significant positive correlation was observed between 8-OHdG levels and intraocular pressure (R=0.284, p=0.008) and cup/disc ratio (R=0.233, p=0.031). Furthermore, in receiver operating characteristic analysis, the area under the curve was statistically significant (p=0.032) with a value of 0.635 (95% CI = 0.518-0.751). CONCLUSION: The study demonstrates an association of increased plasma levels of 8-OHdG in patients with PXG, supporting the role of oxidative stress, and increased oxidative DNA damage in PXG development.