Proliferative vitreoretinopathy (PVR) is a refractory vitreoretinal fibrosis disease, and epithelial‐mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is the key pathological mechanism of PVR. However, few studies focused on the role of METTL3, the dominating methyltransferase for m6A RNA modification in PVR pathogenesis. Immunofluorescence staining and qRT‐PCR were used to determine the expression of METTL3 in human tissues. Lentiviral transfection was used to stably overexpress and knockdown METTL3 in ARPE‐19 cells. MTT assay was employed to study the effects of METTL3 on cell proliferation. The impact of METTL3 on the EMT of ARPE‐19 cells was assessed by migratory assay, morphological observation and expression of EMT markers. Intravitreal injection of cells overexpressing METTL3 was used to assess the impact of METTL3 on the establishment of the PVR model. We found that METTL3 expression was less in human PVR membranes than in the normal RPE layers. In ARPE‐19 cells, total m6A abundance and the METTL3 expression were down‐regulated after EMT. Additionally, METTL3 overexpression inhibited cell proliferation through inducing cell cycle arrest at G0/G1 phase. Furthermore, METTL3 overexpression weakened the capacity of TGFβ1 to trigger EMT by regulating wnt/β ‐catenin pathway. Oppositely, knockdown of METTL3 facilitated proliferation and EMT of ARPE‐19 cells. In vivo, intravitreal injection of METTL3‐overexpressing cells delayed the development of PVR compared with injection of control cells. In summary, this study suggested that METTL3 is involved in the PVR process, and METTL3 overexpression inhibits the EMT of ARPE‐19 cells in vitro and suppresses the PVR process in vivo.

Purpose: The purpose of this study was to investigate the effects of silibinin on epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) and proliferative vitreoretinopathy (PVR) formation, as well as its underlying molecular mechanism. Methods: Cellular morphological change and EMT molecular markers were evaluated by using phase contrast imaging, qPCR, and Western blot (WB) to investigate the impact of silibinin on the EMT of ARPE-19 cells. Scratch assay and transwell assay were used to study the effect of silibinin on cell migration. An intravitreally injected RPE-induced rat PVR model was used to assess the effect of silibinin on PVR in vivo. RNA-seq was applied to study the molecular mechanism of silibinin-mediated PVR prevention. Results: Silibinin inhibited TGFβ1-induced EMT and migration of RPE in a dose-dependent manner in vitro. Moreover, silibinin prevented proliferative membrane formation in an intravitreal injected RPE-induced rat PVR model. In line with these findings, RNA-seq revealed a global suppression of TGFβ1-induced EMT and migration-related genes by silibinin in RPEs. Mechanistically, silibinin reduced TGFβ1-induced phosphorylation levels of Smad3 and Stat3, and Smad3 nuclear translocation in RPE. Conclusions: Silibinin inhibits the EMT of RPE cells in vitro and prevents the formation of PVR membranes in vivo. Mechanistically, silibinin inhibits Smad3 phosphorylation and suppresses Smad3 nuclear translocation through the inhibition of Stat3 phosphorylation. These findings suggest that silibinin may serve as a potential treatment for PVR.

Covalent CDK7 inhibitor THZ1 is a newly discovered anti-tumor drug.THZ1 affects the function of transcription factor TFIIH by inhibiting CDK7, which in turn affects RNA polymerase II, and ultimately affects transcription initiation. Study found that THZ1 could inhibit proliferation and promote apoptosis of several tumor cell lines. However, there is no report of the potential side effect of THZ1 in normal tissues. In the course of cancer, the muscle consumption of cachexia needs to be supplemented by the differentiation of muscle cells. However, the effect of THZ1 on myogenic differentiation remains unclear. Our study in this article found that THZ1 could both inhibit the differentiation of C2C12 cells and mouse primary myoblasts, also repressing the expression of differentiation-related transcription factors and muscle structural proteins, such as and myogenin, myh3 and MCK. Moreover, THZ1 could inhibit C2C12 cell proliferation and migration, increase its oxidative stress and promote its apoptosis. Our data indicates that THZ1 inhibits myogenic differentiation, suggesting that therapies based on THZ1 might have potential side effects on muscle functions.

Purpose. This study aimed to describe and analyze the clinical features of 20 eyes of 15 primary vitreoretinal lymphoma (PVRL) patients. Methods. This was a retrospective case series and a review of the literature. Fifteen PVRL patients (20 affected eyes) referred between February 2011 and December 2019 were recruited, and their medical records were retrospectively reviewed. Results. Among these 15 PVRL patients, seven were men (46.67), and five had bilateral PVRL (33.33). The median onset age was 66±9.26 years and six (40) patients had central nervous system (CNS) involvement, and two of them died of CNS-related complications. The ocular symptoms varied from decreased vision to binocular diplopia. The ocular manifestations were diverse and involved both the anterior and posterior segments, including the vitreous cells, subretinal white-yellow lesions, cotton-wool spots, and ophthalmoplegia. The rate of misdiagnosis and failure to diagnose was 100, and 30 of them were misdiagnosed as uveitis. We found five cases revealing rare characteristics of this malignancy. Among them, there were two cases with mild hypertensive retinopathy exhibiting cotton-wool spots, one case mimicking age-related macular degeneration (AMD), one case with systemic lupus erythematosus (SLE), and one patient had extraocular muscle involvement. To the best of our knowledge, we reported PVRL exhibiting cotton-wool spots as the main manifestation and coexisting with extraocular myopathy for the first time. Conclusions. PVRL is a rare intraocular malignancy that commonly masquerades as uveitis. As the clinical signs and symptoms are atypical, ophthalmologists must carefully examine patients to avoid misdiagnosis or a failure to diagnose. Cotton-wool spots and extraocular myopathy might be the dominant initial symptoms in PVRL patients, and AMD should be considered a differential diagnosis of PVRL. SLE patients under immunosuppressive treatment could have spontaneous PVRL.

Purpose: The aim of this study was to investigate the possible risk factors and prognosis of initial no light perception (NLP) in pediatric open globe injuries (POGI). Procedures: This retrospective, comparative, interventional case-control study included 865 eyes of POGI patients presenting to a tertiary referral ophthalmic center from January 1, 2011 to December 31, 2015. Eyes were divided into 2 groups: the NLP group included eyes with initial NLP, and the light perception (LP) group included eyes with initial LP or vision better than LP. Results: The following risk factors were significantly related to initial NLP: severe intraocular hemorrhage (OR 3.287, p = 0.015), retinal detachment (RD; OR 2.527, p = 0.007), choroidal damage (OR 2.680, p = 0.016), and endophthalmitis (OR 4.221, p < 0.001). Choroidal damage is related to remaining NLP after vitreoretinal surgery (OR 12.384, p = 0.003). At the last visit, more eyes in the NLP group suffered from silicone oil-sustained status (OR 0.266, p = 0.020) or ocular atrophy (OR 0.640, p = 0.004), and fewer eyes benefitted from final LP (OR 41.061, p < 0.001) and anatomic success (OR 4.515, p < 0.001). Conclusion: Severe intraocular hemorrhage, RD, choroidal damage, and endophthalmitis were possible predictors of initial NLP in POGI. Choroidal damage was the major factor related to an NLP prognosis. Traumatized eyes with initial NLP could be anatomically and functionally preserved by vitreoretinal surgery.