Selective microRNA expression of exosomes from retinal pigment epithelial cells by oxidative stress.

The function of exosomal miRNAs (miRs) in retinal degeneration is largely unclear. We were aimed to investigate the functions of exosomes as well as their miRs derived from retinal pigment epithelial (RPE) cells following exposure to oxidative stress (OS). After the OS by lipopolysaccharide and rotenone on RPE cells, interleukin-1 beta (IL-1ß), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α) were upregulated, along with the decreased mitochondrial membrane potential and upregulated oxidative damage marker 8-OH-dG in RPE cells. RPE-derived exosomes were then isolated, identified, injected into the subretinal space in mice. After subretinal injection, RPE-exosomes after OS not only induced higher ROS level and apoptotic retinal cells, but also elevated IL-1ß, IL-6 alongside TNF-α expressions among retina/RPE/choroidal complex. Next, miRs inside the exosomes were sequenced by the next generation sequencing (NGS) technology. NGS revealed that certain miRs were abundant in exosomes, while others were selectively kept by RPE cells. Further, downregulated miRs, like miR-125b-5p, miR-125a-5p, alongside miR-128-3p, and upregulated miR, such as miR-7-5p were validated byRT-qPCR. Finally, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to find the possible target genes of those selective exosomal miRs. Our results proved that the RPE-derived exosomes after OS selectively express certain miRs, providing novel insights into the pathogenesis of age-related macular degeneration (AMD) in future.

Comparisons of Vitreal Angiogenic, Inflammatory, Profibrotic Cytokines, and Chemokines Profile between Patients with Epiretinal Membrane and Macular Hole.

OBJECTIVES: Idiopathic epiretinal membrane (iERM) or idiopathic macular hole (iMH) is frequently used as a "healthy" control in comparison of vitreous cytokines with other vitreoretinal diseases. This study aimed to investigate if there is a difference in vitreal cytokines expression between patients with iERM and iMH. METHODS: In this prospective study, all subjects received standard pars plana vitrectomy surgery, and 0.5 ml of native vitreous sample was extracted during the vitrectomy. Luminex technology and enzyme-linked immunosorbent assay were used to profile the concentration of 52 classic angiogenic, inflammatory, and profibrotic cytokines and chemokines. Statistical analyses were performed by the Mann-Whitney U test, followed by multiple comparisons by the Bonferroni correction. RESULTS: Vitreal samples from 13 iERM and 24 iMH were studied. Of the 52 tested cytokines, 41 were similar in expression, and 5 were under the detection limit, while 6 cytokines (MMP-8, Eotaxin, MIP-1a, RANTES, TGF-ß2, and IL-4) were differently expressed between two groups (p < 0.05). Nevertheless, these significances disappeared after the adjustment of Bonferroni correction. CONCLUSION: The tested cytokines showed similar expression between iERM and iMH patients. This indicates that eyes with iERM or iMH can be together served as "healthy" controls.

PERFLUOROCARBON LIQUID-ASSISTED INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE VERSUS INTERNAL LIMITING MEMBRANE PEELING FOR HIGHLY MYOPIC MACULAR HOLE RETINAL DETACHMENT.

PURPOSE: To compare the efficacy of a modified perfluorocarbon liquid-assisted inverted internal limiting membrane (ILM) flap technique with the standard ILM peeling for the treatment of macular hole retinal detachment in highly myopic eyes. METHODS: This was a retrospective, consecutive, nonrandomized comparative study. Forty-two macular hole retinal detachment eyes of 42 patients were included into either a perfluorocarbon liquid-assisted inverted ILM flap technique group (n = 22, inverted group) or standard ILM removal group (n = 20, peeling group). Outcomes measured were macular hole closure, retinal reattachment, and best-corrected visual acuity at least 6 months after surgery. RESULTS: Macular hole closure was achieved in 20 eyes (90.9%) in the inverted group and in eight eyes (40%) in the peeling group (P < 0.01). Reattachment rates were 100% in the inverted group and 95% in the peeling group (P = 0.476). The mean best-corrected visual acuity improvement from baseline was 27.4 ± 19.9 Early Treatment Diabetic Retinopathy Study letters in the inverted group while the best-corrected visual acuity improvement was 13.6 ± 22.5 Early Treatment Diabetic Retinopathy Study letters in the peeling group (P = 0.044). CONCLUSION: The perfluorocarbon liquid-assisted inverted ILM flap technique was effective in sealing the macular hole, reattaching retina, and improving visual function postoperatively in highly myopic macular hole retinal detachment.

A Potential Mechanism of Temozolomide Resistance in Glioma-Ferroptosis.

Temozolomide (TMZ) is the first-line chemotherapy drug that has been used to treat glioma for over a decade, but the benefits are limited by half of the treated patients who acquired resistance. Studies have shown that glioma TMZ resistance is a complex process with multiple factors, which has not been fully elucidated. Ferroptosis, which is a new type of cell death discovered in recent years, has been reported to play an important role in tumor drug resistance. The present study reviews the relationship between ferroptosis and glioma TMZ resistance, and highlights the role of ferroptosis in glioma TMZ resistance. Finally, the investigators discussed the future orientation for ferroptosis in glioma TMZ resistance, in order to promote the clinical use of ferroptosis induction in glioma treatment.

Minimal internal limiting membrane peeling with ILM flap technique for idiopathic macular holes: a preliminary study.

BACKGROUND: Internal limiting membrane (ILM) peeling increases the idiopathic macular hole (IMH) closure rate but causes the inner retina dimplings. This study is to introduce a method to minimally peel the ILM, and with the ILM flap to ensure the IMH closure. METHODS: Twelve consecutive IMH eyes were treated with the minimal ILM peeling with ILM flap technique. The ILM around the MH is peeled off in an annular shape with a width of approximately 200 to 300 µm. A tongue-shape ILM flap is created in the superior retina and the inferior margin of ILM is not peeled off. The ILM flap is then inverted to cover the MH, followed by fluid-air exchange and air or silicon tamponade. Spectral domain-optical coherence tomography (SD-OCT) and en face OCT for morphological assessment, best corrected visual acuity (BCVA) and multifocal electroretinogram (ERG) for functional evaluation were performed at baseline and at each postoperative follow-up. RESULTS: All the 12 eyes achieved macular hole closure on SD-OCT after surgery (100%). At baseline, the mean preoperative BCVA was 0.83 ± 0.33 and it improved to 0.39 ± 0.28 postoperatively (p <  0.001). En face OCT showed the inner retinal dimplings were localized only in superior ILM-free retinas (7 eyes). The mERG response density in the central (R1), para-central (R2), R1/R2 ring ratios were remarkably improved at the last follow-up (p = 0.001, p = 0.033, p = 0.018, respectively). CONCLUSIONS: The minimal ILM peeling with ILM flap technique can achieve favorable MH closure with less inner retinal dimplings and has promising visual recovery for IMH eyes.

MicroRNA targeting microtubule cross-linked protein (MACF1) would suppress the invasion and metastasis of malignant tumor.

Cancer is one of the most serious diseases that endanger human health in the world today, and the incidence and mortality of cancer increases year by year. Invasion and metastasis is the most prominent feature of malignant tumors, but also becomes the primary factor of threatening patient's health. Tumor cell invasion and metastasis which closely related to the dynamic changes of the cytoskeleton is an important factor influencing the survival of patients. Therefore, inhibition of tumor cell invasion and metastasis is a key strategy for the treatment of cancer. MACF1 is a microtubule microfilament cross-linking factor that plays an important role in cell polarization, cell migration, and maintenance of tissue integrity. A lot of studies have shown that microRNAs play an important role in tumorigenesis, invasion and metastasis. Therefore, we propose the following scientific assumptions: MACF1, an important molecule in adjusting the invasion and metastasis of tumor cells, regulates microfilaments, microtubules participating in cytoskeleton dynamics to promote malignant tumor cell migration and invasion; MicroRNA targeting MACF1 can decrease the expression of MACF1 and thus disrupt the dynamic balance of microtubule or microfilaments as an effective way to inhibit the invasion and metastasis of tumor cells. So we can use it as a new target for clinical early diagnosis and treatment of malignant tumor invasion and metastasis.