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Retinoblastoma (RB) is the most common intraocular malignant tumor in children, primarily attributed to the bi-allelic loss of the RB1 gene in the developing retina. Despite significant progress in understanding the basic pathogenesis of RB, comprehensively unravelling the intricate network of genetics and epigenetics underlying RB tumorigenesis remains a major challenge. Conventional clinical treatment options are limited, and despite the continuous identification of genetic loci associated with cancer pathogenesis, the development of targeted therapies lags behind. This review focuses on the reported genomic and epigenomic alterations in retinoblastoma, summarizing potential therapeutic targets for RB and providing insights for research into targeted therapies.

This study retrospectively analyzes the immune and inflammatory indices of patients with lacrimal-gland benign lymphoepithelial lesion (LGBLEL) in order to screen out reference indices with higher diagnostic efficacy. The medical histories of patients whose diagnoses of LGBLEL and primary lacrimal prolapse were confirmed by pathology between August 2010 and August 2019 were collected. In the LGBLEL group, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, rheumatoid factor (RF), and immunoglobulins G, G1, G2, and G4 (IgG, IgG1, IgG2, IgG4) were higher (p < 0.05) and the expression level of C3 was lower (p < 0.05) compared to the lacrimal-gland prolapse group. Multivariate logistic regression analysis showed that IgG4, IgG, and C3 were independent risk factors for predicting LGBLEL occurrence (p < 0.05). The area under the receiver operating characteristic (ROC) curve of the prediction model (IgG4+IgG+C3) was 0.926, which was significantly better than that of any single factor. Therefore, serum levels of IgG4, IgG, and C3 were independent risk factors for predicting the occurrence of LGBLEL, and the combined diagnostic efficacy of IgG4+IgG+C3 was the highest.

Dry eye syndrome (DES) is a prevalent ocular disorder involving diminishe·d tear production and increased tear evaporation, leading to ocular discomfort and potential surface damage. Inflammation and reactive oxygen species (ROS) have been implicated in the pathophysiology of DES. Inflammation is one core cause of the DES vicious cycle. Moreover, there are ROS that regulate inflammation in the cycle from the upstream, which leads to treatment failure in current therapies that merely target inflammation. In this study, we developed a novel therapeutic nanoparticle approach by growing cerium oxide (Ce) nanocrystals in situ on mesenchymal stem cell-derived exosomes (MSCExos), creating MSCExo-Ce. The combined properties of MSCExos and cerium oxide nanocrystals aim to target the “inflammation-ROS-injury” pathological mechanism in DES. We hypothesized that this approach would provide a new treatment option for patients with DES. Our analysis confirmed the successful in situ crystallization of cerium onto MSCExos, and MSCExo-Ce displayed excellent biocompatibility. In vitro and in vivo experiments have demonstrated that MSCExo-Ce promotes corneal cell growth, scavenges ROS, and more effectively suppresses inflammation compared with MSCExos alone. MSCExo-Ce also demonstrated the ability to alleviate DES symptoms and reverse pathological alterations at both the cellular and tissue levels. In conclusion, our findings highlight the potential of MSCExo-Ce as a promising therapeutic candidate for the treatment of DES.

Diabetic retinopathy (DR) is one of the most common and serious microvascular complications of diabetes. Although current treatments can control the progression of DR to a certain extent, there is no effective treatment for early DR. Apart from vascular endothelial growth factor, it has been noted that the apelin/APJ system contributes to the pathogenesis of DR. We used a high-fat diet/streptozotocin-induced type 2 diabetic mouse model. The mice were divided into a lentivirus control group (LV-EGFP), an apelin-overexpression group (LV-Apelin+), and an apelin-knockdown group (LV-Apelin−), all of which were administrated intravitreal injections. LV-Apelin+ ameliorated the loss of pericytes in DR mice, whereas LV-Apelin− aggravated the loss of pericytes. Similarly, LV-Apelin+ reduced the leakage of retinal vessels, whereas LV-Apelin− exacerbated it. The genes and signaling pathway related to cell adhesion molecules were downregulated, whereas the cell–cell tight junctions and anti-apoptotic genes were upregulated in response to apelin overexpression. However, the alterations of these same genes and signaling pathways were reversed in the case of apelin knockdown. Additionally, LV-Apelin+ increased ZO-1 and occludin levels, whereas LV-Apelin− decreased them. Our results suggest that apelin can reduce vascular leakage by protecting pericytes, which offers a promising new direction for the early treatment of DR.

Purpose: To evaluate the expressions of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in the vitreous and fibrovascular membranes (FVMs) of proliferative diabetic retinopathy (PDR) after the intravitreal injection of ranibizumab (IVR) and further explore the relationship between EPO and VEGF.Method: The concentrations of EPO and VEGF levels in the vitreous fluid were measured in 35 patients (24 PDR and 11 non-diabetic patients) using enzyme-linked immunosorbent assay. The patients were divided into three groups: PDR with IVR (IVR group) before par plana vitrectomy (n = 10), PDR without IVR (Non-IVR group) (n = 14) and a control group [macular holes (MHs) or epiretinal membranes (ERM), n = 11]. Fluorescence immunostaining was performed to examine the expressions of VEGF, EPO and CD 105 in the excised epiretinal membranes.Result: The PDR eyes of Non-IVR group had the highest vitreous VEGF and EPO levels (836.30 ± 899.50 pg/ml, 99.29 ± 27.77 mIU/ml, respectively) compared to the control group (10.98 ± 0.98 pg/ml and 18.96 ± 13.30 mIU/ml/ml). Both the VEGF and EPO levels in the IVR group (13.22 ± 2.72 pg/ml and 68.57 ± 41.47 mIU/ml) were significantly lower than the Non-IVR group (P = 0.004 and P = 0.04, respectively). Furthermore, no significant difference was observed for VEGF levels between the control and IVR groups (10.9 ± 0.98 pg/ml and 13.22 ± 2.72 pg/ml, respectively, P = 0.9). Yet the EPO level in the IVR group was significantly higher than that in the Non-diabetic group (68.57 ± 41.47 pg/ml and 18.96 ± 13.30 pg/ml, respectively, P = 0.001). The expressions of EPO, VEGF, and CD105 were significantly reduced in fluorescence immunostaining of FVMs in the IVR group compared with the Non-IVR group. The receiver operating characteristic (ROC) curve of the EPO and VEGF levels were 0.951 and 0.938 in the PDR group.Conclusion: Both of the VEGF and EPO level were significantly increased in PDR patients, which have equal diagnostic value in the prediction of PDR. IVR could reduce the EPO level, but not enough to the normal level.