Background: Proliferative vitreoretinopathy (PVR) is a blind-causing disease initiated by the activation of retinal pigmented epithelium (RPE) primarily induced by TGF-β families. Migrasome is a recently discovered type of extracellular vesicle related to cell migration. Results: Here, we used ex vivo, in vitro, and in vivo models, to investigate the characteristics and functions of migrasomes in RPE activation and PVR development. Results indicated that the migrasome marker tetraspanin-4 (TSPAN4) was abundantly expressed in human PVR-associated clinical samples. The ex vivo model PVR microenvironment is simulated by incubating brown Norway rat RPE eyecups with TGF-β1. Electron microscope images showed the formation of migrasome-like vesicles during the activation of RPE. Further studies indicated TGF-β1 increased the expression of TSPAN4 which results in migrasome production. Migrasomes can be internalized by RPE and increase the migration and proliferation ability of RPE. Moreover, TSPAN4-inhibited RPE cells are with reduced ability of initiating experimental PVR. Mechanically, TSPAN4 expression and migrasome production are induced through TGF-β1/Smad2/3 signaling pathway. Conclusion: In conclusion, migrasomes can be produced by RPE under PVR microenvironment. Migrasomes play a pivotal role in RPE activation and PVR progression. Thus, targeting TSPAN4 or blocking migrasome formation might be a new therapeutic method against PVR.

Increased oxidative stress, which can lead to the retinal pigment epithelium (RPE) cell death by inducing ATP depletion and DNA repair, is believed to be a prominent pathology in age-related macular degeneration (AMD). In the present study, we showed that and 0.1 mM nicotinamide adenine dinucleotide (NAD⁺) administration significantly blocked RPE cell death induced by 300 μM H₂O₂. Further investigation showed that H₂O₂ resulted in increased intracellular ROS level, activation of PARP-1 and subsequently necrotic death of RPE cells. Exogenous NAD⁺ administration significantly decreased intracellular and intranuclear ROS levels in H₂O₂-treated RPE cells. In addition, NAD⁺ administration to H₂O₂-treated RPE cells inhibited the activation of PARP-1 and protected the RPE cells against necrotic death. Moreover, exogenous NAD⁺ administration up-regulated autophagy in the H₂O₂-treated RPE cells. Inhibition of autophagy by LY294002 blocked the decrease of intracellular and intranuclear ROS level. Besides, inhibition of autophagy by LY294002 abolished the protection of exogenous NAD⁺ against H₂O₂-induced cell necrotic death. Taken together, our findings indicate that that exogenous NAD⁺ administration suppresses H₂O₂-induced oxidative stress and protects RPE cells against PARP-1 mediated necrotic death through the up-regulation of autophagy. The results suggest that exogenous NAD⁺ administration might be potential value for the treatment of AMD.

Despite the remarkable success of immunotherapy in the treatment of melanoma, resistance to these agents still affects patient prognosis and response to therapies. Beta-2-microglobulin (β2M), an important subunit of major histocompatibility complex (MHC) class I, has important biological functions and roles in tumor immunity. In recent years, increasing studies have shown that B2M gene deficiency can inhibit MHC class I antigen presentation and lead to cancer immune evasion by affecting β2M expression. Based on this, B2M gene defect and T cell-based immunotherapy can interact to affect the efficacy of melanoma treatment. Taking into account the many recent advances in B2M-related melanoma immunity, here we discuss the immune function of the B2M gene in tumors, its common genetic alteration in melanoma, and its impact on and related improvements in melanoma immunotherapy. Our comprehensive review of β2M biology and its role in tumor immunotherapy contributes to understanding the potential of B2M gene as a promising melanoma therapeutic target.

Inflammation and immune reaction have a strong link with the pathology of glaucoma especially AACG. Some cytokines may act as biomarkers to evaluate the severity of glaucoma. Anti-inflammatory treatments and controlling of IOP are necessary for the therapy of glaucoma.

Purpose To compare the intraoperative and postoperative clinical properties of 1% ropivacaine, 0.75% bupivacaine, 2% lidocaine and a mixture of 0.75% bupivacaine and 2% lidocaine (bupi+lido) administered for peribulbar anaesthesia during vitrectomy. Methods A total of 140 patients were randomly allocated to four groups. The time of onset of analgesia and akinesia was measured. The efficacy of anaesthesia, degree of postoperative pain and intraoperative and postoperative complications were recorded. Results The mean times of onset (±SD) of analgesia for the ropivacaine, bupivacaine, lidocaine and lido+bupi groups were 90.46±30.08, 94.83±40.72, 78.31±12.56 and 101.51±56.94 s, respectively (p=0.087). The mean times of onset (±SD) of akinesia for the ropivacaine, bupivacaine, lidocaine and lido+bupi groups were 138.89±62.65, 151.86±84.78, 122.66±49.35 and 141.54±62.69 s, respectively (p=0.323). No significant difference was observed in the number of patients who attained grade-5 anaesthesia in the four groups (p=0.966). The outcome of ordered logit analysis showed that the 1% ropivacaine resulted in a significantly lower degree of postoperative pain compared with the other three groups (p=0.017, p=0.001 and p=0.001, respectively). The incidence of postoperative subconjunctival haemorrhage was decreased in the ropivacaine group compared with the other three groups (p<0.001). Conclusions For peribulbar anaesthesia in vitrectomy, 1% ropivacaine alone provides an adequate intraoperative anaesthesia similar to that provided by the bupivacaine, lidocaine and lido+bupi solutions, as well as provides a better quality of postoperative analgesia and decreases postoperative subconjunctival haemorrhage. Trial registration number ChiCTR-IPR-16007876; Results.