BMP4 aggravates mitochondrial dysfunction of HRMECs.

Mitochondria are important places for the oxidative phosphorylation of glucose and the maintenance of cell oxidation and antioxidant stability. However, mitochondrial dysfunction causes cell dysfunction. Meanwhile, retinal vascular endothelial cell dysfunction may cause vascular inflammation, hemorrhage, angiogenesis, and other manifestations. Our previous studies have shown that Bone morphogenetic protein 4 (BMP4) is an important target for the treatment of retinal neovascularization, but the mechanism remains unclear. Therefore, our study aims to observe the effects of BMP4 on vascular endothelial cells and hopes to provide a new target for diabetic retinopathy. 4-Hydroxynonenal (4HNE), a kind of lipid peroxide, was used to induce the oxidative stress model. Human retinal microvascular endothelial cells (HRMECs) were randomly divided into control, 4HNE, negative control, and siBMP4 groups. Si-BMP4 significantly reduced leukocyte adhesion and 4HNE-induced high ROS level and restored the mitochondrial membrane potential and OCR. This indicates that BMP4 plays an important role in inducing leukocyte adhesion, oxidative stress, and mitochondrial dysfunction. The relationship between BMP4 and retinal vascular endothelial cell dysfunction is preliminarily confirmed by this study. Mitochondrial dysfunction and oxidative stress may be involved in BMP4-mediated retinal vascular endothelial cell dysfunction.

The role of optical coherence tomography angiography in distinguishing ischemic versus non-ischemic central retinal vein occlusion.

INTRODUCTION: To observe macular microvascular changes in patients with ischemic and non-ischemic central retinal vein occlusion (CRVO) by optical coherence tomography angiography (OCTA), and explore the value of OCTA in differentiating ischemic and non-ischemic CRVO. METHODS: Cross sectional study. Fifty patients diagnosed as CRVO with macular edema were included. Macular edema in all patients were regressive after three consecutive anti-VEGF treatment. Patients were divided into ischemic and non-ischemic group according to ultra-wide-angle fundus fluorescein angiography (UWFFA). All patients underwent BCVA, IOP, color fundus photography, UWFFA and OCTA. The following parameters were measured: (1) Vessel density (VD): superficial and deep whole VD (SVD, DVD), superficial and deep central fovea VD (SFVD, DFVD), superficial and deep parafoveal VD (SPFVD, DPFVD); (2) Central foveal retinal thickness (CRT); (3) Area of foveal avascular zone (FAZ), perimeter of FAZ (PERIM), avascular index of FAZ (AI) and VD within a width of 300 microns around the FAZ region (FD-300). Comparison between ischemic and non-ischemic group was performed by two independent sample t-tests. Receiver operating characteristic (ROC) curve analysis was used to measure the area under the curve (AUC) of VD for predicting ischemic CRVO. RESULTS: There were no significant differences in IOP, SFVD, DFVD and CRT between ischemic and non-ischemic group, and significant differences in age, BCVA, SVD, SPFVD, DVD, DPFVD, FAZ area, PERIM, AI and FD-300 between ischemic and non-ischemic group. ROC curve analysis showed AUC of DVD and DPFVD in predicting ischemic CRVO was highest (0.962). the threshold was 38.40%, and the sensitivity was 100%, but the specificity of DVD (92.3%) was significantly higher than that of DPFVD (84.6%). Therefore, DVD ≤ 38.40% can be used as the best threshold for determining ischemic CRVO. CONCLUSION: OCTA can quantitatively evaluate the macular microvascular structure of CRVO, which is helpful to distinguish ischemic from non-ischemic CRVO.

Cytokine levels in the aqueous humor of young and senior patients with proliferative diabetic retinopathy.

OBJECTIVE: To evaluate the aqueous humor levels of vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF), and tumor necrosis factor α (TNF-α) as biomarkers of the severity of proliferative diabetic retinopathy (PDR) in young and senior patients. METHODS: This was a prospective clinical study. From October 2020 to June 2021, 37 patients (37 eyes) who were diagnosed with PDR and received pars plana vitrectomy (PPV) at Tianjin Medical University Eye Hospital were recruited and allocated to either the young (16 patients, 16 eyes) or senior subgroup (21 patients, 21 eyes). Twelve patients with cataracts (12 eyes) who underwent phacoemulsification combined with intraocular lens (IOL) implantation during the same period were recruited in the control group. The fibrovascular proliferation (FVP) grade and PDR severity scores were recorded during PPV. Enzyme-linked immunosorbent assay was used to detect the levels of VEGF, CTGF, and TNF-α in the aqueous humor. RESULTS: (1) Young patients with PDR had a higher FVP grade and PDR severity score (P = 0.037, = 0.009); (2) The levels of the three cytokines in the study group were all significantly higher than in the control group (all P < 0.001); (3) The CTGF level in the young subgroup (2239.55 ± 167.32 pg/mL) was significantly higher than that in the senior subgroup (2114.49 ± 102.04 pg/mL) (P = 0.025). The VEGF level in the young subgroup (311.09 ± 10.74 pg/mL) was significantly lower than that in the senior subgroup (324.85 ± 14.97 pg/mL) (P = 0.004). The TNF-α level was not statistically different between the two subgroups (P = 0.382); (4) The CTGF/VEGF ratio in the young subgroup (7.20 ± 0.54) was significantly higher than in the senior subgroup (6.52 ± 0.39) (P < 0.001); (5) The CTGF/VEGF ratio was positively correlated with the FVP grades (R = 0.377, P = 0.022) and with the PDR severity scores (R = 0.354, P = 0.032) in patients with PDR. CONCLUSION: The aqueous humor CTGF/VEGF ratio was positively correlated with the severity of PDR. A higher CTGF/VEGF ratio in the aqueous humor proved that neovascular fibrosis was more serious in young patients when they received PPV.

Research progress of UWFFA and OCTA in retinal vein occlusion: A review.

Retinal vein occlusion (RVO) is a retinal vascular disease that severely impairs the visual function of patients. Observing the changes of retinal blood vessels before and after treatment is of great significance for the prognostic evaluation of RVO. The rapid development and widespread use of fundus imaging technique, especially ultra-wide-angle fundus fluorescein angiography (UWFFA) and optical coherence tomography angiography (OCTA) have made our observation of the retinal blood vessels of RVO more comprehensive and meticulous. In this paper, we reviewed the latest research progress of UWFFA and OCTA in RVO.