Isorhamnetin suppresses the epithelial-mesenchymal transition of the retinal pigment epithelium both in vivo and in vitro through Nrf2-dependent AKT/GSK-3ß pathway.

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly worldwide. Multiple studies have shown that epithelial-mesenchymal transition (EMT) plays a pivotal role in the pathogenesis of AMD. Isorhamnetin (Isor) is a flavonoid compound that inhibits EMT in tumor cells. However, whether it can also attenuate EMT in the retinal pigment epithelium (RPE) is unknown. Therefore, our study was designed to probe the possible impact of Isor on EMT process in both mouse retina and ARPE-19 cells. C57BL/6 mice were utilized to establish a dry AMD model. Isor and LCZ (a mixture of luteine/ß-carotene/zinc gluconate) were administered orally for 3 months. The effects of Isor on the retina were evaluated using fundus autofluorescence, optical coherence tomography, and transmission electron microscopy. Transwell and wound healing assay were employed to assess ARPE-19 cell migration. Western blotting and immunofluorescence were used to measure the protein expressions associated with EMT, Nrf2 and AKT/GSK-3ß pathway. The findings indicated that Isor alleviated dry AMD-like pathological changes in vehicle mice retina, inhibited the migration of Ox-LDL-treated ARPE-19 cells, and repressed the EMT processes in vivo and in vitro. Furthermore, Isor activated Nrf2 pathway and deactivated AKT/GSK-3ß pathway in both vehicle mice and ARPE-19 cells. Interestingly, when Nrf2 siRNA was transfected into ARPE-19 cells, the inhibitory effect of Isor on EMT and AKT/GSK-3ß pathway was attenuated. These results suggested that Isor inhibited EMT processes via Nrf2-dependent AKT/GSK-3ß pathway and is a promising candidate for dry AMD treatment.

Evaluation of phacoemulsification (ultrasound) cataract surgery on the dynamics of the anterior segment of primary angle closure by AS-OCT.

OBJECTIVE: To explore the changes of anatomical biological parameters and dynamic parameters of the anterior segment (AS) before and after primary angle closure glaucoma (PACG) surgery. METHODS: The clinical data of 82 patients (82 eyes) who underwent phacoemulsification in our hospital were retrospectively analyzed and divided into group A (angle closure, n = 38) and group B (normal open angle, n = 44). The anatomical biological parameters and dynamic parameters were compared between the two groups before and after surgery. RESULTS: Compared with group B, group A had smaller anterior chamber depth, higher vaulting, greater iris curvature, and smaller TISA500. Compared with group B, group A had smaller ΔTISA500 and ΔI-area. Compared with group B, the TISA500 was smaller in group A preoperatively, at 1 week, and 1 month after surgery (P < 0.05). The iris curvature was larger in group A (P < 0.05). The ΔI-area was significantly reduced in group B at 1 week and 1 month after surgery. Group B exhibited smaller ΔI-curv than group A at 1 week and 1 month after surgery (P < 0.05). CONCLUSION: Anterior segment optical coherence tomography (AS-OCT) can effectively monitor the dynamic changes (DC) of the AS caused by phacoemulsification in patients with primary angle closure (PAC). Phacoemulsification can open the primary of PAC patients. However, their iris area does not change significantly. The biological characteristics of the iris itself may be a risk factor leading to PAC.

Therapeutic Effect of Abelmoschus manihot on Type 2 Diabetic Nonproliferative Retinopathy and the Involvement of VEGF.

OBJECTIVE: To evaluate the efficacy of Abelmoschus manihot in treating type 2 diabetic nonproliferative retinopathy. METHODS: It was a randomized controlled clinical trial. The recruited eighty subjects with type 2 diabetic nonproliferative retinopathy were randomly divided into treatment group and control group. The two groups received basic treatments including control of blood glucose, blood pressure and blood lipid, management of diet, exercise and health education, and monitoring of relevant indicators. Additionally, the treatment group was given oral administration of Abelmoschus manihot. All subjects were followed up on monthly basis for consecutive six months. The related parameters including diabetic retinopathy (DR) incidence rates, "Early Treatment Diabetic Retinopathy Study" (ETDRS) vision scores, retinal thicknesses in macular region, serum vascular endothelial growth factor (VEGF) levels, and biochemical indicators of both groups before and after treatment were accurately collected and statistically analyzed. RESULTS: There were no significant differences of DR severity levels, ETDRS vision scores, macular retinal thicknesses such as cube average thickness (CAT), central subfield thickness (CST), and cube volume (CV), and serum VEGF levels between two groups before treatment. Meanwhile, there were no significant differences of demographic characteristics, case terminations, blood glucose, blood lipid, blood pressure, biochemical indicators of hepatorenal function, hypoglycemic drugs, hypotensive drugs, and other basic treatments between two groups during six months treatment. The present study suggested that the remission rate of DR and the ETDRS vision score in the treatment group were significantly higher than those of the control group (remission rate: 25.4% vs 9.3%, P=0.01; ETDRS score: 78 (72, 82) vs 72 (67, 80), P=0.0002) while the progression rate of DR in the treatment group was significantly lower than that of the control group (progression rate: 4.2% vs 18.7%, P=0.007) after six months treatment. In addition, the CAT, CST, CV, and serum VEGF levels of the treatment group were significantly improved after the treatment (CAT: 286 (278, 302) vs 282 (270, 295) µm, P < 0.0001; CST: 251 (239, 274) vs 248 (235, 265) µm, P < 0.0001; CV: 10.3 (10.0, 10.9) vs 10.1 (9.7, 10.6) mm3, P < 0.0001; VEGF: 0.21 (0.14, 0.58) vs 0.16 (0.10, 0.23) ng/ml, P=0.0026), while there were no significant differences of the control group before and after treatment (CAT: 287 (279, 294) vs 287 (279, 295) µm, P=0.27; CST: 250 (240, 266) vs 252 (238, 266) µm, P=0.72; CV: 10.4 (10.1, 10.6) vs 10.4 (10.1, 10.7) mm3, P=0.53; VEGF: 0.21 (0.13, 0.66) vs 0.23 (0.12, 0.64) ng/ml, P=0.85). CONCLUSION: The study offered the novel evidence for the therapeutic effect of Abelmoschus manihot on type 2 diabetic nonproliferative retinopathy, which was associated with improved VEGF. This trial is registered with ChiCTR1800019292.

Macular abnormality observed by OCT in children with amblyopia failing to achieve normal visual acuity after long-term treatment.

PURPOSE: To investigate why some children with amblyopia fail to achieve normal visual acuity. METHODS: Optical coherence tomography (OCT) was perform to observe the morphology of the macular tissue of children with various types of amblyopia who failed to achieve normal visual acuity (< or = 20/25). Average thickness of the retinal nerve fiber layer (RNFL) of the foveola and fovea (1-mm diameter range) was then assessed by macular retinal tomography map measurement. The data obtained were compared with those considered normal to detect any abnormality. RESULTS: Fifteen patients (24 eyes) were examined. Images showed abnormality with thickness RNFL in the macular area in which

Macular Abnormality Observed by Optical Coherence Tomography in Children with Amblyopia Failing to Achieve Normal Visual Acuity After Long-Term Treatment.

PURPOSE:To investigate why some children with amblyopia fail to achieve normal visual acuity. METHODS:Optical coherence tomography (OCT) was performed to observe the morphology of the macular tissue of children with various types of amblyopia who failed to achieve normal visual acuity (