Recently, a wide range of biological and pathological roles of long noncoding RNAs (lncRNAs) have been discovered. However, the potential role of circulating lncRNAs H19 and GAS5 in type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) is not clear. Here, we assessed the plasma levels of H19 and GAS5 lncRNAs in T2DM patients with/without DR and evaluated if H19 and GAS5 pre-treatment plasma levels are a predictor of early response to a single aflibercept dose in DR subgroup. Plasma lncRNA expression profiles of 119 T2DM patients (66 with DR and 53 without DR) and 110 healthy controls were determined by quantitative reverse transcription PCR. The association of lncRNA expression profiles with clinical features and aflibercept early response in DR patients was investigated. Relative H19 expression levels were significantly increased in T2DM group (including DR and non-DR subgroups) vs. controls, while GAS5 levels were decreased in T2DM group (p < 0.001).
Background: Long non-coding RNAs (lncRNAs) play essential roles in molecular diagnosis and therapeutic response in several diseases. Purpose: For the first time, we aimed to evaluate the association of four lncRNAs TUG1 (rs7284767G/A), MIAT (rs1061540T/C), MALAT1 (rs3200401C/T), and SENCR (rs12420823C/T) variants with susceptibility to diabetic retinopathy (DR), disease severity, and early therapeutic response to intravitreous anti-vascular endothelial growth factor aflibercept therapy. Patients and Methods: This case-control study enrolled 126 adult patients with type 2 diabetes. TaqMan assays using Real-Time PCR were run for genotyping. Multivariable regression analyses were applied to assess the role of each polymorphism after the adjustment of covariates. Results: Carriers of TUG1 A/G and MIAT T/C and C/C genotypes were more likely to develop DR [OR=3.15 (95% CI=1.15-8.64), and OR=4.31 (95% CI=1.78-10.47)], while MALAT1 T/C conferred protection (OR=0.40, 95% CI=0.16-0.99). For TUG1, MALAT1, MIAT, and SENCR genotype combinations, GTCT and GCCC had a higher disease risk (P=0.012). For disease severity, MIAT T/T homozygosity was associated with higher DR grade [33.3% (T/T) vs 10% (C/C) and 4.2% (C/T) carriers, P=0.012]. Otherwise, patients with the SENCR T variant exhibited better pre-treatment best-corrected visual acuity level (p=0.021). Following aflibercept administration, carrying the TUG1 A or MIAT T/C was associated with a poor therapeutic response (OR=5.02, 95% CI=1. and OR=10.23, respectively). Conclusion:The lncRNAs TUG1 (rs7284767G/A) and MIAT (rs1061540T/C) were associated with increased DR susceptibility and poor response to aflibercept treatment, while MALAT1 (rs3200401C/T) conferred protection to DR. These genetic determinants could be useful in DR risk stratification and pharmacogenetics after validation in large-scale studies.
Purpose: To investigate for the first time the association of collagen COL4A3 (rs55703767), COL5A1 (rs7044529), and COL4A4 (rs2229813) variants with response to corneal collagen cross-linking (CXL) with riboflavin and ultraviolet A in patients with keratoconus (KC). Methods: A total of 147 eligible patients with KC were genotyped for the specified collagen variants using real-time TaqMan-based polymerase chain reaction. Adjusted odds ratio (OR) with 95% confidence interval (CI) was applied to assess the strength of the association with response to CXL for a decrease in maximum keratometry and/or an increase in corneal thickness. Results: Eighty-two patients (55.8%) had post-CXL successful outcomes. The overall analysis revealed that minor allele frequencies of COL4A3, COL5A1, and COL4A4 variants were 0.22, 0.22, and 0.38, respectively. The G/T genotype of the COL4A3 variant was more prevalent in the successful group (43%) compared with the failure group (23%) (P < 0.001). COL4A3 (rs55703767) was associated with a good response under heterozygote (OR: 2.19, 95% CI, 1.04–4.59, P < 0.001) and overdominant (OR: 2.59, 95% CI, 1.25–5.38, P = 0.008) models. By contrast, COL5A1 and COL4A4 variants were not associated with the effective response after CXL treatment. Interestingly, stratification analysis by sex revealed that CXL was more successful in female patients with KC under heterozygote (OR: 4.71, 95% CI, 1.74–12.75), dominant (OR: 3.16, 95% CI, 1.29–7.78), and overdominant (OR: 5.18, 95% CI, 1.92–13.95) models for COL4A3 (rs55703767) variant. Conclusions: The COL4A3 (rs55703767) variant, among other study variants, could be implicated in CXL riboflavin/ultraviolet A treatment response in patients with KC in the study population. Large-scale replication and follow-up studies in different ethnic groups are warranted.
Purpose. To assess eye pressure, ganglion cell complex, and retinal nerve fiber layer changes following cataract surgery in patients with pseudoexfoliation glaucoma. Methods. Eighty-five patients with pseudoexfoliation glaucoma (PEXG) were included in the study. They were divided into two groups; the first group included patients with PEXG and cataract who underwent phacoemulsification (pseudophakic group; n = 40 eyes). The second group included patients with PEXG without cataract (control group; n = 45 eyes). Both groups were on antiglaucoma treatment. IOP changes after surgery and the ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (pRNFL) thicknesses were evaluated in patients underwent cataract extraction surgery compared to controls that did not have cataract, nor underwent surgery. Both groups were followed up postoperatively for 18 months. Results. There was no difference in the mean age and glaucoma stage in both groups (P=0.242 and 0.70, respectively). In the pseudophakic group, the mean IOP significantly dropped from 20.43 ± 0.90 to 17.00 ± 2.75 mmHg at the end of the follow-up period (P≤0.001). Slight decrease (≈3 μm) was recorded in the mean GCC thickness of the pseudophakic patients from the baseline at the end of the follow-up period. This decrease was lower than that of the controls (≈5 μm). No significant pRNFL changes were recorded all over the postoperative visits (88.78 ± 22.55 μm at 3 months, 88.67 ± 23.14 μm at 6 months, 87.62 ± 23.04 μm at 12 months, and 87.32 ± 22.61 μm at 18 months) as compared to preoperative value (90.28 ± 22.31 μm) with P=0.335, 0.387, 0.158, and 0.110, respectively, or controls (89.69 ± 21.76 μm, 88.73 ± 21.08 μm, 87.33 ± 20.67 μm, and 87.23 ± 20.54 μm with P=0.850, 0.990, 0.951, and 0.984). Conclusion. Phacoemulsification and IOL implantation may aid in managing pseudoexfoliation glaucoma by lowering IOP and slowing the rate of GCC and pRNFL losses over a short-term period.
Introduction: Diabetic retinopathy (DR) is one of the major vision-threatening causes worldwide. Searching for an individualized therapeutic strategy to prevent its progress is challenging. Objective: This work aimed to investigate the association of angiogenesis-inducer vascular endothelial growth factor (VEGF) gene family and related receptor variants (rs833069, rs12366035, rs7664413, rs7993418, and rs2305948) with susceptibility of DR and the response to 1 dose of aflibercept treatment in type 2 diabetes mellitus (T2DM). Methods: Consecutive eligible patients with T2DM (n = 125) and 110 unrelated controls were enrolled in this preliminary prospective case-controlled study. Genotyping was identified using TaqMan real-time PCR. Adjusted odds ratio (OR) with 95% confidence interval (CI) was applied to assess the strength of the association with the clinical/ophthalmological characteristics and early response to intravitreal aflibercept treatment in terms of improved visual acuity (BCVA) and central macular thickness (CMT). Results: We found that both VEGFB rs12366035 and VEGFC rs7664413 conferred higher risk for DR progression under allelic (OR [95% CI]: 1.71 [1.07–2.74]), homozygote comparison (3.55 [1.32–9.57]), and recessive (3.77 [1.43–9.93]) models for the former and under allelic (2.09 [1.25–3.490, homozygote comparison (2.76 [1.02–7.45]), and recessive (2.62 [0.98–6.98] models for the latter. In contrast, VEGFR1 rs7993418 conferred protection against DR under heterozygote comparison and dominant models. The rs12366035*T/T genotype showed the worst pretreatment BCVA score (0.35 ± 0.24) compared to other corresponding genotypes (0.66 ± 0.26 in C/T and 0.54 ± 0.25 in C/C carriers) (p = 0.008). Meanwhile, patients with rs7993418*G/G of VEGFR1 exhibited a significant reduction in CMT after aflibercept injection (12.26 ± 35.43 µ in G/G vs. 3.57 ± 8.74 µ in A/A) (p = 0.037). Conclusions: Polymorphisms of the studied VEGF/receptors could be considered as genetic risk factors of DM/DR development and could play an important role in aflibercept early response for DR patients in the study population.
The study was investigated to evaluate the potentials of using Ascophyllum nodosum (Kelp meal, a Canadian commercial product form of that seaweed) as a natural feed additive through evaluating its effect on the growth performance, blood parameters, and meat quality of Broad Breasted Bronze (BBB a heavy strain selected line) commercial turkeys. Thirty-four imported BBB turkeys at 10 weeks of age were divided randomly into three treatments with two replicates (with unequal numbers in some of these replicates). All birds were fed a basal diet (Control, C) and two groups (i.e. treatments 2& 3) were having their diets additionally supplemented with A. nodosum (Kelp) at 1% and 2% from 10 until marketing at 21wks. of age. Body weight, gain in weight and feed conversion have been generally improved, but feed intake has been slightly decreased by feeding those turkey broilers on the Kelp supported diets. Feeding on the tested seaweed diet improved significantly (P≤ 0.05) the percentage of eviscerated weight. Diets supported additionally with A. nodosum recorded generally the best blood parameters and meat quality measures compared to control. Both levels of Kelps seaweed supplementation (i.e. treatments 2& 3) recorded the lowest blood figures, in varying degrees, of total proteins, AST, ALT, triglycerides, cholesterol and creatinine levels; while recorded the highest blood values, at miscellaneous extents, of albumin and globulin. Significant treatment effects (P 0.05 or P 0.01) were detected on liver and blood uric acid and meat color quality (i.e. thigh meat lightness, thighs and breast meat redness and yellowness colors). It seemed from the results that Kelp meal (A. nodosum) supplementation up to 2%, (i.e. treatments 2& 3), to basal diets would beneficially support growth performance, blood parameters, and meat quality of BBB turkey broilers. These effects are likely to make A. nodosum acts as promising potential growth promoter.
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