Eupatilin attenuates TGF-ß2-induced proliferation and epithelial-mesenchymal transition of retinal pigment epithelial cells.

PURPOSE: The main characteristic of proliferative vitreoretinopathy (PVR) is migration, adhesion, and epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPE). Eupatilin is a naturally occurring flavone that has the potential to inhibit cell proliferation and EMT. However, its efficacy on the PVR model induced by transforming growth factor-2 (TGF-ß2) is unknown. In this study, the potential effect of eupatilin on proliferation and EMT in the treatment of RPE was investigated. METHODS: Serum starved human RPE cells (ARPE-19) were treated with 10 ng/ml TGF-ß2 alone or co-treated with 25 µM eupatilin for 48 h. Quantitative real-time PCR and Western blot analysis were used to assess targets at the mRNA and protein expression level, respectively. Apoptosis and cell cycle progression was assessed by image-based cytometry. The effect of treatment on cell migration was evaluated by wound healing assay. RESULTS: Eupatilin inhibited TGF-ß2-induced RPE cell proliferation via regulating the cell cycle and inducing apoptosis. TGF-ß2 upregulated mRNA expression of mesenchymal markers fibronectin and vimentin was significantly downregulated by the treatment, while the epithelial markers E-cadherin and occludin expression was upregulated. The therapy significantly suppressed TGF-ß2 encouraged cell migration through downregulating the expression of transcription factors Twist, Snail, and ZEB1 induced by TGF-ß2. Furthermore, eupatilin significantly inhibited the expression of MMP-1, -7, and -9, and suppressed NF-κB signalling. CONCLUSION: These results suggest that eupatilin could inhibit the proliferation and transformation into fibroblast-like cells of RPE cells; thus the agent may be a potential therapeutic value in treating PVR.

Corneal epithelium and limbal region alterations due to glaucoma medications evaluated by anterior segment optic coherence tomography: a case-control study.

AIM: To investigate the corneal epithelial and limbal epithelial alterations in patients under topical glaucoma treatment using anterior segment-OCT (AS-OCT) and to determine the changes of the limbal region due to the preservatives and glaucoma drugs, that can progress to limbal stem cell deficiency (LSCD). Limbal thickness was measured by AS-OCT to evaluate limbal cell deficiency. METHODS: Forty-seven patients using topical medication for glaucoma, and 48 control subjects were enrolled in this matched case-control study. The patients were divided into four groups according to the treatment regimens. Group 1: One-drug regimen, Group 2: Two-drug regimen, Group 3: Three-drug regimen, Group 4: Four-drug regimen For the ocular surface evaluation; tear break-up time with standard fluorescein sodium sterile strip application, Schirmer test-I, Ocular Surface Disease Index Questionnaire, and AS-OCT were performed. RESULTS: A total of 95 subjects were included: 47 eyes of 47 patients with glaucoma medication and 48 eyes of 48 healthy subjects. There was a statistically significant difference between patients and controls according to BUT, SCH, and OSDI (p < 0.001). The mean central corneal epithelium thickness was 48.5 ± 5.3 in patients and 54.5 ± 5.9 in controls (p < 0.001). The mean central total corneal thickness was 529.2 ± 41.2 in patients and 536 ± 35.3 in controls (p = 0.335). The mean limbal epithelium thickness was 64.1 ± 9.1 in patients and 76 ± 11.5 in controls (p < 0.001). CONCLUSION: Using at least one glaucoma drug caused limbal area injury, changed ocular surface measurements, and significantly reduced the limbal epithelial thickness where the stem cells reside. The limbal epithelial thickness measurement by AS-OCT seems to be an innovative, non-invasive, and promising technique for detecting and staging corneal damage in topical glaucoma therapy.

NATURAL COURSE OF VITREOMACULAR TRACTION IN EYES WITH DIABETIC RETINOPATHY AND FACTORS ASSOCIATED WITH SPONTANEOUS RELEASE.

PURPOSE: The aim of this study was to determine the natural course of vitreomacular traction (VMT) in patients with diabetic retinopathy and to evaluate the factors associated with VMT relief. METHODS: Seventy-four eyes of 65 patients with VMT accompanying diabetic retinopathy were evaluated retrospectively. The presence of intravitreal injection and the presence of panretinal photocoagulation were obtained from the medical records of the patients. Spontaneous release of VMT, the horizontal length of vitreomacular traction, the presence of hyperreflective retinal spots, the presence of the epiretinal membrane, and the grade of VMT were evaluated from the spectral-domain optical coherence tomography images. Factors associated with the spontaneous release of VMT were evaluated by logistic regression analysis. RESULTS: Spontaneous release was observed in 28 eyes (37.8%). The horizontal length of VMT was lower in the release of the VMT group compared with the persistent VMT group (P = 0.03). The persistent VMT group had a higher rate of hyperreflective retinal spots and epiretinal membrane compared with the release of the VMT group (respectively; P = 0.003 and P = 0.031). No statistically significant difference was observed between the release of VMT and persistent VMT groups in terms of intravitreal injection and panretinal photocoagulation treatment (respectively; P = 0.938 and P = 0.36). The absence of hyperreflective retinal spots was the most important prognostic factor for the spontaneous release of VMT (P = 0.029). CONCLUSION: Spontaneous release of VMT observed higher rates of patients without hyperreflective retinal spots, epiretinal membrane, and patients with lower horizontal length of VMT.