Retinoblastoma (RB) is a highly aggressive paediatric ophthalmological malignancy that commonly affects the eyes of children under 5 years old and is responsible for 5% of blindness in children. 1,2 Retinoblastoma initiation occurs with exceptionally high efficiency in response to the loss of functional pRB protein, which is encoded by the RB1 gene. 3 Retinoblastoma is derived from the immature

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Selective covalent CDK7 inhibitor THZ1 is a promising potential anti-tumor drug in many kinds of cancers. Epithelial-mesenchymal Transition (EMT) is highly related to cancer initiation, development, invasion and metastasis and other pathogenesis processes. We treated cancer cell line Hela229 and three retinoblastoma cell lines so-RB50, WERI-Rb-1, Y79 with gradient concentration of THZ1, and found that THZ1 could inhibit cell viability and EMT, suggesting that THZ1 may be a promising drug for human cervical cancer and retinoblastoma treatment. Our results verified the role of THZ1 in EMT for the first time, however, the mechanism needs further study. Here we report that THZ1 suppresses the TGFβ2 induced EMT in human SRA01/04 lens epithelial cells (LECs), rabbit primary lens epithelial cells, and whole rat lens culture semi-in vivo model. RNA-sequencing and KEGG analysis revealed that the THZ1 inhibits EMT by down-regulating phosphorylate Smad2 and Notch signaling pathway. On the other hand, we found that THZ1 could strongly inhibit LECs proliferation through G2/M phase arrest as well as attenuating of MAPK, PI3K/AKT signaling pathway. Our results uncovered the function and underlying mechanism of THZ1 in regulation of EMT, which provides a new perspective of the anti-tumor effect by THZ1 and may offer a novel treatment for PCO.

Age-related macular degeneration (AMD) is a leading cause of blindness and progressive loss of central vision in the elderly population. The important factor of AMD pathogenesis is the degeneration of retinal pigment epithelial (RPE) cells by oxidative stress. Inactivation of PTEN can disrupt intercellular adhesion in the RPE cells, but the mechanism of oxidative stress is less known. Here we presented evidence that UVB-mediated oxidative stress induced apoptosis in ARPE-19 cells. Downregulation of the expression of PTEN in UVB-irradiative RPE cells triggered DNA damage and increased the level of UVB-induced apoptosis by activating p53-dependent pathway. However, overexpression of PTEN increased cell survival by suppressing p-H2A in response to DNA damage and apoptosis. When using Pifithrin-α (one of p53 inhibitors), the level of p53-dependent apoptosis was significantly lower than untreated, which suggested that p53 was possibly involved in PTEN-dependent apoptosis. Thus, it elucidated the molecular mechanisms of UVB-induced damage in RPE cells and may offer an alternative therapeutic target in dry AMD.

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.

Firework-related eye injury is a horrible medical problem and creates huge health and social burdens. Herein, we explored the changing trends and demographic and clinical features of firework-related eye injury, in an effort to inform strategies to prevent this injury. We reviewed the data of 468 hospitalized patients who underwent surgery for firework-related eye injury at the Zhongshan Ophthalmic Center between January 2013 and December 2017. During this period, the trend in firework-related eye injuries was stable (mean, 93 ± 14 cases per year), and fireworks were the major cause of explosive eye injury. The average age of the patients was 24 ± 18 years and 87% of the patients were male, with boys under 10 years of age comprising the largest group (27% of patients). There were an average of 24 ± 7 cases per year from urban areas and 70 ± 8 cases from rural areas (P<0.05). Furthermore, 21 ± 5% of cases occurred during Spring Festival. After treatment, the best corrected visual acuity was increased compared to that before treatment, and the intraocular pressure tended to become normal by the final visit (P<0.05). The top three diagnoses were cataract (39%), retinal detachment (18%), and choroidal detachment (14%). Additionally, the most common surgery was cataract extraction (25%), followed by pars plana vitrectomy (19%) and pars plana vitrectomy plus pars plana lensectomy (10%). Over the five-year study period, day surgery hospitalization increased from 1% to 32%. This was associated with a corresponding decrease in the length of hospitalization, without adverse events, demonstrating that day surgery is feasible in firework-related eye injury cases. The present study results suggest that greater attention should be paid to firework-related eye injury, and a variety of measures should be taken to prevent this kind of ocular tragedy.

αB-Crystallin, a member of the small heat shock protein (sHSP) family, plays an immunomodulatory and neuroprotective role by inhibiting microglial activation in several diseases. However, its effect on endotoxin-induced uveitis (EIU) is unclear. Autophagy may be associated with microglial activation, and αB-crystallin is involved in the regulation of autophagy in some cells. The role of αB-crystallin in microglial autophagy is unknown. This study aimed to explore the role of αB-crystallin on retinal microglial autophagy, microglial activation, and neuroinflammation in both cultured BV2 cells and the EIU mouse model. Our results show that αB-crystallin reduced the release of typical proinflammatory cytokines at both the mRNA and protein level, inhibited microglial activation in morphology, and suppressed the expression of autophagy-related molecules and the number of autophagolysosomes in vitro. In the EIU mouse model, αB-crystallin treatment alleviated the release of ocular inflammatory cytokines and the representative signs of inflammation, reduced the apoptosis of ganglion cells, and rescued retinal inflammatory structural and functional damage, as evaluated by optical coherence tomographic and electroretinography. Taken together, these results indicate that αB-crystallin inhibits the activation of microglia and supresses microglial autophagy, ultimately reducing endotoxin-induced neuroinflammation. In conclusion, αB-crystallin provides a novel and promising option for affecting microglial autophagy and alleviating symptoms of ocular inflammatory diseases.

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