Knockdown of HSPA13 Inhibits TGFβ1-Induced Epithelial-Mesenchymal Transition of RPE by Suppressing the PI3K/Akt Signaling Pathway.

Purpose: This study aimed to explore the impact of HSPA13 on epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells and proliferative vitreoretinopathy (PVR) development, along with its associated molecular mechanisms.

Methods: HSPA13 expression was evaluated in epiretinal membranes (ERMs) from patients with PVR using immunohistochemistry. The effects of HSPA13 knockdown on TGFβ1-induced EMT in hESC-RPE cells were studied through quantitative PCR (qPCR), Western blot, and wound healing assays.

SUMOylation of GMFB regulates its stability and function in retinal pigment epithelial cells under hyperglycemia.

Background: Glia maturation factor beta (GMFB) is a growth and differentiation factor that acts as an intracellular regulator of signal transduction pathways. The small ubiquitin-related modifier (SUMO) modification, SUMOylation, is a posttranslational modification (PTM) that plays a key role in protein subcellular localization, stability, transcription, and enzymatic activity. Recent studies have highlighted the importance of SUMOylation in the inflammation and progression of numerous diseases.

The identification of a novel shared therapeutic target and drug across all insulin-sensitive tissues under insulin resistance.

Background: To identify key and shared insulin resistance (IR) molecular signatures across all insulin-sensitive tissues (ISTs), and their potential targeted drugs.

Methods: Three datasets from Gene Expression Omnibus (GEO) were acquired, in which the ISTs (fat, muscle, and liver) were from the same individual with obese mice. Integrated bioinformatics analysis was performed to obtain the differentially expressed genes (DEGs).

Wnt5a/β-catenin-mediated epithelial-mesenchymal transition: a key driver of subretinal fibrosis in neovascular age-related macular degeneration.

Background: Neovascular age-related macular degeneration (nAMD), accounts for up to 90% of AMD-associated vision loss, ultimately resulting in the formation of fibrotic scar in the macular region. The pathogenesis of subretinal fibrosis in nAMD involves the process of epithelial-mesenchymal transition (EMT) occurring in retinal pigment epithelium (RPE). Here, we aim to investigate the underlying mechanisms involved in the Wnt signaling during the EMT of RPE cells and in the pathological process of subretinal fibrosis secondary to nAMD.

GMFB/AKT/TGF-β3 in Müller cells mediated early retinal degeneration in a streptozotocin-induced rat diabetes model.

Retinal degeneration, characterized by Müller cell gliosis and photoreceptor apoptosis, is considered an early event in diabetic retinopathy (DR). Our previous study proposed that GMFB may mediate diabetic retinal degeneration. This study identified GMFB as a sensitive and functional gliosis marker for DR.

Subconjunctival injection of human umbilical cord mesenchymal stem cells alleviates experimental allergic conjunctivitis via regulating T cell response.

Background: T helper 2 (Th2) cells are thought to play critical roles in allergic conjunctivitis (AC). They release inflammatory cytokines to promote an allergic response in AC. Due to individual heterogeneity and long-term chronic management, current therapies do not always effectively control AC.

Molecular pathogenesis of subretinal fibrosis in neovascular AMD focusing on epithelial-mesenchymal transformation of retinal pigment epithelium.

Age-related macular degeneration (AMD) is a leading cause of vision loss among elderly people in developed countries. Neovascular AMD (nAMD) accounts for more than 90% of AMD-related vision loss. At present, intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is widely used as the first-line therapy to decrease the choroidal and retinal neovascularizations, and thus to improve or maintain the visual acuity of the patients with nAMD.

Comprehensive Bibliometric Analysis of Stem Cell Research in Alzheimer's Disease from 2004 to 2022.

Introduction: Stem cell-based regenerative medicine has provided an excellent opportunity to investigate therapeutic strategies and innovative treatments for Alzheimer's disease (AD). However, there is an absence of visual overviews to assess the published literature systematically.

Methods: In this review, the bibliometric approach was used to estimate the searched data on stem cell research in AD from 2004 to 2022, and we also utilized CiteSpace and VOSviewer software to evaluate the contributions and co-occurrence relationships of different countries/regions, institutes, journals, and authors as well as to discover research hot spots and encouraging future trends in this field.

Aquaporin 11 alleviates retinal Müller intracellular edema through water efflux in diabetic retinopathy.

Retinal Müller glial dysfunction and intracellular edema are important mechanisms leading to diabetic macular edema (DME). Aquaporin 11 (AQP11) is primarily expressed in Müller glia with unclear functions. This study aims to explore the role of AQP11 in the pathogenesis of intracellular edema of Müller glia in diabetic retinopathy (DR).

Inflammation in diabetic retinopathy: possible roles in pathogenesis and potential implications for therapy.

Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components.

Induced retinal pigment epithelial cells with anti-epithelial-to-mesenchymal transition ability delay retinal degeneration.

The hostile microenvironment of the retina in patients with age-related macular degeneration (AMD) may trigger epithelial-to-mesenchymal transition (EMT) of grafted retinal pigment epithelial (RPE) cells, thus attenuating the therapeutic outcome. Here, we transformed human dedifferentiated induced pluripotent stem cell-derived RPE (iPSC-RPE) cells into induced RPE (iRPE) cells using a cocktail of four transcription factors (TFs)-CRX, MITF-A, NR2E1, and C-MYC. These critical TFs maintained the epithelial property of iRPE cells by regulating the expression of , forkhead box f2, , and , and conferred resistance to TGF-β-induced EMT in iRPE cells by targeting .

Direct conversion of human umbilical cord mesenchymal stem cells into retinal pigment epithelial cells for treatment of retinal degeneration.

Age-related macular degeneration (AMD) is a major vision-threatening disease. Although mesenchymal stem cells (MSCs) exhibit beneficial neural protective effects, their limited differentiation capacity in vivo attenuates their therapeutic function. Therefore, the differentiation of MSCs into retinal pigment epithelial (RPE) cells in vitro and their subsequent transplantation into the subretinal space is expected to improve the outcome of cell therapy.

Human amniotic epithelial cell-derived extracellular vesicles provide an extracellular matrix-based microenvironment for corneal injury repair.

To study the biological functions and applications of human amniotic epithelial cell-derived extracellular vesicles (hAEC-EVs), the cargos of hAEC-EVs were analyzed using miRNA sequencing and proteomics analysis. The hAECs and hAEC-EVs in this study had specific characteristics. Multi-omics analyses showed that extracellular matrix (ECM) reorganization, inhibition of excessive myofibroblasts, and promotion of target cell adhesion to the ECM were their primary functions.

Anti-VEGF reduces inflammatory features in macular edema secondary to retinal vein occlusion.

Aim: To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in patients with macular edema secondary to retinal vein occlusion (RVO-ME).

Methods: Twenty-eight eyes from twenty-eight treatment-naïve patients (14 males and 14 females) with RVO-ME were included in this retrospective study. The retinal vein occlusion (RVO) was comprised of both central retinal vein occlusion (CRVO, =14) and branch retinal vein occlusion (BRVO, =14).

Elimination of senescent cells inhibits epithelial-mesenchymal transition of retinal pigment epithelial cells.

Age-related macular degeneration (AMD) is one of the most common leading causes of irreversible blindness, and there is no effective treatment for it. It has been reported that aging is the greatest risk factor for AMD, and epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells plays an important role in the pathogenesis of AMD. To clarify the relationship between senescence and EMT in RPE cells, we used the replicative senescence model, HO- and/or Nutlin3a-induced senescence model, and low-density and/or TGF-β-induced EMT model to detect the expression of senescence-, RPE- and EMT-related genes, and assessed the motility of cells by using a scratch wound migration assay.

Hyperreflective Foci in Diabetic Macular Edema with Subretinal Fluid: Association with Visual Outcomes after Anti-VEGF Treatment.

Introduction: Objectives of the study were to describe the hyperreflective foci (HRF) on optical coherence tomography angiography in diabetic macular edema (DME) with subretinal fluid (SRF) and explore the association of HRF in the outer retina with photoreceptor integrity and visual outcomes after anti-vascular endothelial growth factor (anti-VEGF) treatment.

Methods: We retrospectively reviewed 46 eyes (36 patients) with DME treated with anti-VEGF drugs. The following parameters, including best-corrected visual acuity (BCVA), central macular thickness (CMT), the height of SRF, the number of HRF in the superficial capillary plexus, deep capillary plexus, and the outer retina, as well as the integrity of external limiting membrane (ELM) and ellipsoid zone (EZ), were evaluated and compared between the baseline and after 2 monthly injections of anti-VEGF drugs.

Melatonin Maintains Inner Blood-Retinal Barrier by Regulating Microglia Inhibition of PI3K/Akt/Stat3/NF-κB Signaling Pathways in Experimental Diabetic Retinopathy.

Microglial activation and melatonin protection have been reported in diabetic retinopathy (DR). Whether melatonin could regulate microglia to protect the inner blood-retinal barrier (iBRB) remains unknown. In this study, the role of microglia in iBRB breakdown and the mechanisms of melatonin's regulation on microglia were explored.

Chaperone-mediated autophagy plays an important role in regulating retinal progenitor cell homeostasis.

Purpose: To explore the function and regulatory mechanism of IFITM3 in mouse neural retinal progenitor cells (mNRPCs), which was found to be very important not only in the development of the retina in embryos but also in NRPCs after birth.

Methods: Published single-cell sequencing data were used to analyze IFITM3 expression in mNRPCs. RNA interference was used to knock down the expression of IFITM3.

Glia maturation factor-β induces ferroptosis by impairing chaperone-mediated autophagic degradation of ACSL4 in early diabetic retinopathy.

Diabetic retinopathy (DR) is one of the leading causes of blindness in the world, and timely prevention and treatment are very important. Previously, we found that a neurodegenerative factor, Glia maturation factor-β (GMFB), was upregulated in the vitreous at a very early stage of diabetes, which may play an important role in pathogenesis. Here, we found that in a high glucose environment, large amounts of GMFB protein can be secreted in the vitreous, which translocates the ATPase ATP6V1A from the lysosome, preventing its assembly and alkalinizing the lysosome in the retinal pigment epithelial (RPE) cells.

CHIR99021 balance TGFβ1 induced human corneal endothelial-to-mesenchymal transition to favor corneal endothelial cell proliferation.

Corneal endothelial cells (CECs) play a major role in the maintenance of stromal hydration via the barrier and pump function for clear vision. Adult CECs cannot regenerate after injury. CECs cultured in vitro can undergo mitosis but may undergo corneal endothelial-to-mesenchymal transition (EnMT) and lose their endothelial characteristics.

Enhancing fractalkine/CX3CR1 signalling pathway can reduce neuroinflammation by attenuating microglia activation in experimental diabetic retinopathy.

The concept of diabetic retinopathy (DR) has been extended from microvascular disease to neurovascular disease in which microglia activation plays a remarkable role. Fractalkine (FKN)/CX3CR1 is reported to regulate microglia activation in central nervous system diseases. To characterize the effect of FKN on microglia activation in DR, we employed streptozotocin-induced diabetic rats, glyoxal-treated R28 cells and hypoxia-treated BV2 cells to mimic diabetic conditions and explored retinal neuronal apoptosis, reactive oxygen species (ROS), as well as the expressions of FKN, Iba-1, TSPO, NF-κB, Nrf2 and inflammation-related cytokines.

Small-Molecule Induction Promotes Corneal Endothelial Cell Differentiation From Human iPS Cells.

Corneal endothelial cells (CECs) serve as a barrier and foothold for the corneal stroma to maintain the function and transparency of the cornea. Loss of CECs during aging or disease states leads to blindness, and cell replacement therapy using either donated or artificially differentiated CECs remains the only curative approach. Human induced pluripotent stem cells (hiPSCs) that were cultured in chemically defined medium were induced with dual-SMAD inhibition to differentiate into neural crest cells (NCCs).