(-)-Epicatechin Provides Neuroprotection in Sodium Iodate-Induced Retinal Degeneration.

Oxidative stress, mitochondrial impairment, and pathological amyloid beta (Aß) deposition are involved in the pathogenesis of dry age-related macular degeneration (AMD). The natural flavonoid (-)-epicatechin (EC) is known to be an antioxidant and neuroprotective compound. Whether EC plays a therapeutic role in AMD is unknown. In this work, we aimed to assess the efficacy and molecular mechanisms of EC against sodium iodate (NaIO3)-induced retinal degeneration in C57BL/6 mice via bioinformatic, morphological, and functional methods. We demonstrated that EC had no toxic effects on the retina and could ameliorate retinal deformation and thinning. EC treatment prevented outer retinal degeneration, reduced drusen-like deposits, increased b-wave amplitude in electroretinography, blocked retinal gliosis, and increased the number and quality of mitochondria. Importantly, EC increased the protein expression of OPA1 and decreased the expression of PINK1, indicating the role of EC in mitochondrial fusion that impaired by NaIO3. Moreover, EC downregulated APP and TMEM97 levels, upregulated PGRMC1 levels, and reduced subretinal Aß accumulation. This study illustrated that EC, which may become a promising therapeutic strategy for AMD, prevented NaIO3-induced retinal degeneration, and this improvement may be associated with the mitochondrial quality control and the TMEM97/PGRMC1/Aß signaling pathway.

Transplantation of reprogrammed peripheral blood cells differentiates into retinal ganglion cells in the mouse eye with NMDA-induced injury.

The generation of patient-specific induced pluripotent stem cells (iPSCs) holds significant implications for replacement therapy in treating optic neuropathies such as glaucoma. Stem-cell-based therapy targeted at replacing and replenishing retinal ganglion cells is progressing at a fast pace. However, clinical application necessitates an efficient and robust approach for cell manufacturing. Here, we examine whether the embryo body derived from human peripheral blood-derived iPSC can localize into the host retina and differentiate into retinal ganglion cells after transplantation into a glaucoma injury model. Human peripheral blood T cells were isolated and reprogrammed into an induced pluripotent stem cell (TiPSC) line using Sendai virus transduction carrying transcription factors Sox2, Klf4, c-Myc, and Oct4. TiPSCs were differentiated into RGC using neural basal culture. For in vivo studies, embryo bodies derived from TiPSCs (TiPSC-EB) were injected into the vitreous cavity of N-Methyl-d-aspartic acid (NMDA)-treated mice 2 weeks before sacrifice and retinal dissection. Induced pluripotent stem cells generated from human peripheral blood T cells display stem cell morphology and pluripotency markers. Furthermore, RGC-like cells differentiated from TiPSC exhibit extending axons and RGC marker TUJ1. When transplanted intravitreally into NMDA-treated mice, embryo bodies derived from TiPSC survived, migrated, and incorporated into the retina's GCL layer. In addition, TiPSC-EB transplants were able to differentiate into TUJ1 positive RGC-like cells. Retinal ganglion cells can be differentiated using human peripheral blood cells derived iPSC. Transplantation of embryo body derived from TiPSCs into a glaucoma mouse model could incorporate into host GCL and differentiate into RGC-like cells.

CXC Chemokines as Therapeutic Targets and Prognostic Biomarkers in Skin Cutaneous Melanoma Microenvironment.

BACKGROUND: Skin Cutaneous Melanoma (SKCM) is a tumor of the epidermal melanocytes induced by gene activation or mutation. It is the result of the interaction between genetic, constitutional, and environmental factors. SKCM is highly aggressive and is the most threatening skin tumor. The incidence of the disease is increasing year by year, and it is the main cause of death in skin tumors around the world. CXC chemokines in the tumor microenvironment can regulate the transport of immune cells and the activity of tumor cells, thus playing an anti-tumor immunological role and affecting the prognosis of patients. However, the expression level of CXC chemokine in SKCM and its effect on prognosis are still unclear. METHOD: Oncomine, UALCAN, GEPIA, STRING, GeneMANIA, cBioPortal, TIMER, TRRUST, DAVID 6.8, and Metascape were applied in our research. RESULT: The transcription of CXCL1, CXCL5, CXCL8, CXCL9, CXCL10, and CXCL13 in SKCM tissues were significantly higher than those in normal tissues. The pathological stage of SKCM patients is closely related to the expression of CXCL4, CXCL9, CXCL10, CXCL11, CXCL12, and CXCL13. The prognosis of SKCM patients with low transcription levels of CXCL4, CXCL9, CXCL10, CXCL11, and CXCL13 is better. The differential expression of CXC chemokines is mainly associated with inflammatory response, immune response, and cytokine mediated signaling pathways. Our data indicate that the key transcription factors of CXC chemokines are RELA, NF-κB1 and SP1. The targets of CXC chemokines are mainly LCK, LYN, SYK, MAPK2, MAPK12, and ART. The relationship between CXC chemokine expression and immune cell infiltration in SKCM was closed. CONCLUSIONS: Our research provides a basis for screening SKCM biomarkers, predicting prognosis, and choosing immunotherapy.

Construction of immune-related risk signature for uveal melanoma.

Uveal melanoma (UM) is the most frequent primary ocular tumour among adults. Here, we aimed to establish the immune cell-based signature to predict the overall survival (OS) of UM patients. The mRNA profile and matched clinical records of 80 UM patients were downloaded from The Cancer Genome Atlas (TCGA) database. CIBERSORT was used to verify the immune cell types of individuals. The univariate analysis found the CD8+ T cell, monocyte, CD4+ memory T cell (resting) and mast cell (resting) were significantly associated with the OS of UM patients. Subsequently, the LASSO Cox regression test was applied to establish the signature, by which the patients were separated into high- and low-risk subgroups. The Kaplan-Meier analyses found for these patients in the high-risk group had a poor survival rate than those in the low-risk group. The predictive value and stability were confirmed by the receiver operative characteristics curves. Pathway analyses found that the differentially expressed genes between the high- and low-risk subgroups were mainly centralised on immune response-related pathways. Further, the comparison of our signature with clinicopathological records confirmed its superiority and independence. In summary, we established an immune cell-based prognosis-predicting signature for UM patients, which will benefit the individual's treatment.

Increased Levels of DKK1 in Vitreous Fluid of Patients with Pathological Myopia and the Correlation between DKK1 Levels and Axial Length.

Purpose: Dickkopf 1 (DKK1) functions as a natural antagonist of the canonical Wnt/ß-catenin pathway. The purpose of this study was to examine the expression of DKK1 in vitreous samples of patients with pathological myopia, in order to search for possible correlations between DKK1 and axial length.Materials and Methods: The expression of DKK1 and other cytokines in vitreous samples of 44 non-myopic eyes, 42 eyes with low-to-moderate myopia, and 51 eyes with pathological myopia were examined using multiplex cytokine detection technology. Ophthalmologic characteristics, including axial length and subfoveal choroidal thickness, were clinically measured for further analysis.Results: The intravitreous levels of DKK1 (P < .0001) were markedly higher in the pathological myopia group than in the control group. There were no differences of DKK1 levels in different vitreoretinal conditions. Additionally, we found that the DKK1 levels were positively correlated with HGF (ß = 0.268, P = .032), and TIMP-3 (ß = 0.209, P = .047) levels, as well as with axial length (ß = 0.714, P < .0001) in the pathological myopia group.Conclusions: Elevated levels of DKK1 were found in the eyes with elongated axial length.

Systemic Approach to Prevent Inadvertent Perfusion in Eyes with Extensive Choroidal Detachment, Suprachoroidal Fluid, and Hypotony During Pars Plana Vitrectomy.

INTRODUCTION: Rhegmatogenous retinal detachment (RRD) with extensive choroidal detachment (CD), suprachoroidal fluid (SCF), and lower intraocular pressure (IOP) markedly increase the difficulty of pars plana vitrectomy (PPV) because it makes the insertion and placement of the trocar cannulas for PPV time-consuming and technically challenging. In this study, we developed a systemic approach that avoids the risks of sclerotomy or using a longer trocar to help in the safe placement of the trocar cannulas in order to prevent inadvertent fluid/air perfusion during PPV in RRD eyes with extensive CD, SCF, and hypotony. METHODS: This is a prospective case series study. Consecutive patients diagnosed with RRD with extensive CD, SCF, and hypotony were recruited. The main steps included injecting transconjunctival intravitreal fluid to increase IOP and enable the passive egress of SCF into the subconjunctival space, creating and broadening the inner opening for the trocar cannulas, transillumination with an endoillumination light pipe, and indentation of the infusion cannula to create maximum visual exposure of the inner segment and help peripheral shaving around the infusion tip. MAIN OUTCOMES: the success rate of the infusion placement into the vitreous cavity, surgical duration, intra- and postoperative complications, and functional and anatomical outcomes. RESULTS: Thirty-eight patients (38 eyes) were included. The first-time success rate of cannula placement into the vitreous cavity was 100%, with a mean surgical duration of 8.5 ± 1.8 min. No intra- or postoperative complications related to the approach were observed. Significant vision improvement was noted in 68.4% (26/38) of the patients at the final follow-up. The primary and final retinal reattachment rates were 94.7% (36/38) and 100% (38/38), respectively. CONCLUSION: This systemic approach is a feasible option to ensure the safe placement of trocar cannulas and prevent inadvertent perfusion during small-gauge PPV in RRD eyes with extensive CD, SCF, and hypotony, without the need for a draining sclerotomy, a longer trocar, or a sharp clearing of the cannula tip.

The Prevalence and Associations of Peripheral Retinopathy: Baseline Study of Guangzhou Office Computer Workers.

PURPOSE: To determine the prevalence of peripheral retinopathy and its associated risk factors among a sample of Guangzhou office computer workers. METHODS: A cross-sectional study of Guangzhou Chinese computer workstations and operators in different departments and units of the Guangzhou Power Supply Bureau, China, in 2016. Peripheral retinopathy was recorded and analyzed using a scanning laser ophthalmoscope (SLO; Optos, Daytona, United Kingdom) and slit-lamp microscopy combined with a three-mirror contact lens. RESULTS: The 1934 eyes of 967 subjects (513 females and 454 males) were included in this study. In total, 79.1% of the eyes were myopic in workers aged 20-29 years, 72.9% in workers aged 30-39 years, 62.2% in workers aged 40-49 years, and 43.4% in workers aged 50-59 years (p < 0.001). Most eyes had optic nerve crescents (81.3%). Various peripheral degenerations were found: 7 eyes (0.4%) had microcystoid degeneration, 40 (2.1%) had peripheral pigmentary degeneration, 87 (4.5%) had lattice degeneration, and 4 (0.2%) had snail-track degeneration. Nineteen (1.0%) eyes had paving-stone degeneration, 11 (0.6%) eyes had a retinal hole or tear, and 16 (0.8%) eyes had chorioretinal degeneration. Multivariate regression confirmed that greater axial length (OR: 1.18 (1.03, 1.35), p=0.012) and more serious spherical equivalent (OR: 0.82 (0.77, 0.88), p < 0.001) were significant risk factors for peripheral retinal changes. CONCLUSION: Peripheral retinal degenerative changes were found in a larger proportion of younger computer workers than older ones. Myopia is occurring in younger and younger people, accompanied by peripheral retinal degeneration.

Pars plana vitrectomy with partial tamponade of filtered air in Rhegmatogenous retinal detachment caused by superior retinal breaks.

BACKGROUND: To investigate the anatomic and functional outcomes of pars plana vitrectomy (PPV) with partial tamponade of filtered air for rhegmatogenous retinal detachment (RRD) caused by superior retinal breaks. METHODS: Retrospective, comparative, consecutive case series study. Patients with RRD caused by superior retinal breaks undergone PPV with partial tamponade (Group A) and whole tamponade (Group B) of filtered air were included. The main outcomes were primary and final success rates, best corrected visual acuity (BCVA), and rate of postoperative cataract surgery. RESULTS: Forty-one patients (41 eyes) were included in Group A and 36 patients (36 eyes) were included in Group B. There were no significant differences in primary or final success rates between Groups A and B (P = 0.618 and P = 1.000, respectively). The patients in Group A experienced quicker postoperative vision improvement (from the Week 1 follow-up) than the patients in Group B (from the Month 3 follow-up). The postoperative cataract surgery rate of Group A (7/31) was lower than that of Group B (13/26) (P = 0.031). CONCLUSIONS: PPV with partial tamponade of air is effective in achieving a high anatomic success rate, quicker postoperative vision improvement, and lower rate of postoperative cataract surgery in RRD caused by superior retinal breaks.