Objective Mendelian randomization (MR) was used to analyze the potential relationship between blood pressure and proliferative diabetic retinopathy (PDR). MethodsTwo-sample MR analysis was performed using summary statistics from genome-wide association studies. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were selected as the exposure, PDR as the outcome. The instrumental variable of SBP and DBP came from the publicly available data of the the UK Medical Research Council Comprehensive Epidemiology Unit and Neale Laboratory; the outcome data (8 681 cases in the case group, 204 208 cases in the control group, European population) are from the FinnGen database. Inverse variance weighting (IVW) and weighted median (WM) were used to analyze the potential relationships between SBP, DBP and PDR. ResultsMR analysis showed that IVW [SBP: odds ratio (OR)=1.36, 95% confidence interval (CI) 1.17-1.57, P=4.22E-05; DBP: OR=1.29, 95%CI 1.11-1.51, P=8.6E-04], WM (SBP: OR=1.33, 95%CI 1.07-1.66, P=0.009; DBP: OR=1.28, 95%CI=1.03-1.59, P=0.002). The results showed that elevated SBP and DBP increased the risk of PDR. ConclusionBlood pressure (SBP, DBP) change is positively correlated with the risk of PDR.
Objective To observe the effect of bone forming protein 4 (BMP4) on the proliferation and migration of human retinal pigment epithelium (RPE) cells under oxidative stress, and to preliminarily explore its effect on epithelial-mesenchymal transition (EMT) of RPE cells. MethodsHuman RPE cells cultured in vitro were divided into normal group, pure 4-hydroxynonenal (HNE) group (4-HNE group), 4-HNE+NC group and 4-HNE+ small interfering BMP (siBMP4) group. The effect of 4-HNE on the proliferation of RPE cells was detected by thiazole blue colorimetry. The effects of 4-HNE and BMP4 on cell migration were determined by cell scratch test. The expression of BMP4 was detected by immunofluorescence staining, Western blot and real-time quantitative polymerase chain reaction. The transfection efficiency of siBMP4 was observed by fluorescence microscopy. Mitochondrial reactive oxygen species (MitoSOX) were detected by flow cytometry. The expression of EMT markers E-cadherin and Fibronection were detected by immunofluorescence assay. t-test was used for comparison between the two groups, and one-way analysis of variance was used for comparison between the three groups. ResultsCompared with normal group, cell proliferation and migration ability of 4-HNE group were significantly enhanced, with statistical significance (t=21.619, 24.469; P＜0.05). The expression of BMP4 in cells was significantly increased, and the difference was statistically significant (t=19.441, P＜0.05). The relative expression levels of BMP4 mRNA and protein were also significantly increased, with statistical significance (t=26.163, 37.163; P＜0.05). After transfection with siBMP4 for 24 h, the transfection efficiency of BMP4 in RPE cells was＞90%. Compared with 4-HNE group and 4-HNE+NC group, the relative expression levels of BMP4 protein (F=27.241), mRNA (F=36.943), cell mobility (F=46.723) and MitoSOX expression levels (F=39.721) in normal group and 4-HNE+siBMP4 group were significantly decreased. The differences were statistically significant (P＜0.05). The epithelial marker E-cadherin increased significantly, while the mesenchymal marker Fibronection decreased significantly, with statistical significance (F= 51.722, 45.153; P＜0.05). ConclusionsBMP4 inhibits RPE proliferation and migration under oxidative stress. BMP4 is involved in inducing EMT in RPE cells.
Objective To observe the clinical efficacy of pars plana vitrectomy (PPV) combined with dexamethasone intravitreal implant (DEX) in the treatment of proliferative diabetic retinopathy (PDR). MethodsA prospective randomized controlled study. A total of 57 PDR patients with 79 eyes diagnosed by Department of Ophthalmology of The First Affiliated Hospital of Nanjing Medical University from May 2021 to February 2023 were included in the study. Best corrected visual acuity (BCVA) and optical coherence tomography (OCT) were performed in all affected eyes. Central macular thickness (CMT) was measured by OCT. The patients were randomly divided into control group and experimental group, with 27 cases and 35 eyes and 30 cases and 44 eyes, respectively. All eyes were treated with routine 25G PPV and intraoperative whole-retina laser photocoagulation. At the end of the operation, the experimental group was given 0.7 mg DEX intravitreal injection. At 1, 4, 12, and 24 weeks after operation, the same equipment and methods were used for relevant examinations. The improvement after surgery was assessed according to the diabetic retinopathy severity score (DRSS). Mixed analysis of variance was used to compare logarithm of the minimum angle of resolution BCVA and CMT between the two groups and within the two groups before and after operation. ResultsAt 1, 4, 12 and 24 weeks after surgery, BCVA was significantly improved at different time points after surgery, and the differences were statistically significant (P＜0.001). At different time after operation, BCVA in experimental groups was significantly better than that in control group, with statistical significance (P＜0.001). Compared with the CMT before surgery, the CMT at no time point after surgery in experimental group was significantly decreased, and the difference was statistically significant (P ＜0.05). There was no significant difference one week after eye operation in control group (P=0.315). At 4, 12 and 24 weeks after operation, CMT decreased, and the differences were statistically significant (P＜0.05). Compared with before surgery, DRSS increased two steps higher at 1, 4, 12 and 24 weeks after surgery in 20 (45.45%, 20/44), 26 (59.10%, 26/44), 32 (72.73%, 32/44) and 31 (70.45%, 31/44) eyes in the experimental groups, respectively. The control group consisted of 15 (42.86%, 15/35), 15 (42.86%, 15/35), 16 (45.71%, 16/35) and 18 (51.43%, 18/35) eyes, respectively. There was no significant difference in DRSS at 1, 4 and 24 weeks after operation between the control group and the experimental group (P=0.817, 0.178, 0.105). At 12 weeks after surgery, the difference was statistically significant (P=0.020). ConclusionPPV combined with intravitreal injection of DEX in the treatment of PDR can improve postoperative visual acuity, alleviate postoperative macular edema and improve the severity of DR.