cryopreservation-human-embryonic-stem-cell-derived-retinal-pigment

Cryopreservation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells at the Optimal Stage

Retinal pigment epithelial&#160;(RPE) cells derived from human embryonic stem cells (hESCs) are superior cell sources for cell replacement therapy in ...

Shanghai Jiao Tong University School of Medicine

National Clinical Research Center for Eye Diseases

Shanghai Clinical Research Center for Eye Diseases

Shanghai Key Clinical Specialty

Shanghai Key Laboratory of Ocular Fundus Diseases

Shanghai Engineering Center for Visual Science and Photomedicine

Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases

Inflammatory status of RPE cells induced by A2E is essential in the development of AMD. Recent research indicated T-cell immunity was involved in the pathological progression of AMD. This study was designed to investigate how A2E suppresses immunoregulatory function of RPE cells in T-cell immunity in vitro.

A2E Suppresses Regulatory Function of RPE Cells in Th1 Cell Differentiation Via Production of IL-1β and Inhibition of PGE2.

The wet form of age-related macular degeneration (AMD) is a leading cause of blindness among elderly Americans and is characterized by abnormal vessel growth, termed choroidal neovascularization (CNV). Integrin α5β1 is a transmembrane receptor that binds matrix macromolecules and proteinases to stimulate angiogenesis. We recently demonstrated that integrin α5β1 plays a critical role in the development of choroidal neovascularization. In this study, we determined the role and underlying mechanisms of integrin α5β1 in angiogenesis in human choroidal endothelial cells and evaluated the antiangiogenic effects of delivering a combination therapy of ATN-161, an integrin α5β1 inhibitor, and an anti-VEGF monoclonal antibody to rats with laser-induced CNV. Vascular endothelial growth factor (VEGF) is a signaling protein that stimulates vasculogenesis and angiogenesis through a pathway that is distinct from the integrin α5β1 signaling pathway. Our results indicate that fibronectin binds to integrin α5β1 and synergizes VEGF-induced angiogenesis via two independent signaling pathways, FN/integrin α5β1/FAK/ERK1/2 and FN/integrin α5β1/FAK/AKT. Integrin α5 knockdown by shRNA inhibits endothelial cell migration, tube formation, and proliferation, while ATN-161 only partially decreases integrin α5 function. Treatment with ATN-161 combined with anti-VEGF antibody showed joint effects in attenuating angiogenesis. In summary, our results provide the first evidence for the mechanisms by which integrin α5β1 is involved in ocular pathological neovascularization in vivo, suggesting that dual inhibition of integrin α5β1 and VEGF may be a promising novel therapeutic strategy for CNV in wet AMD.

Joint Antiangiogenic Effect of ATN-161 and Anti-VEGF Antibody in a Rat Model of Early Wet Age-Related Macular Degeneration.

The development of diabetic retinopathy has been implicated as a consequence of chronic inflammation. Given the role of the intercellular adhesion molecule-1 (ICAM-1) in inflammation, the potential effect of N-glycosylation on the upregulated expression of ICAM-1 at the surface of bovine retinal endothelial cells (BRECs) induced by high glucose concentrations was investigated.

The role of N-glycosylation in high glucose-induced upregulation of intercellular adhesion molecule-1 on bovine retinal endothelial cells.

More and more concerns have been arisen about the ability of new medical graduates to meet the demands of today's practice environment. In this study, we wanted to develop a valid, reliable and standardized assessment tool for evaluating the basic microsurgical skills of residents in a microsurgery laboratory, to get them well prepared before entering the surgical realm of ophthalmology.

Development of a new valid and reliable microsurgical skill assessment scale for ophthalmology residents.

To investigate different tamponade effects of intravitreal silicone oil (SO) and sterilized air on macular vasculature and structure after successful retinal repair for macular-on rhegmatogenous retinal detachment (RRD) patients.

Comparison of fundus changes following silicone oil and sterilized air tamponade for macular-on retinal detachment patients.

To investigate the vascular density of the optic nerve head (ONH) and macula using optical coherence tomography angiography (OCTA) in patients undergoing vitrectomy for rhegmatogenous retinal detachment (RRD) and to evaluate associations with visual outcomes.

Peripapillary Vessel Density in Eyes with Rhegmatogenous Retinal Detachment after Pars Plana Vitrectomy.

Photoreceptor death and neurodegeneration is the leading cause of irreversible vision loss. The inflammatory response of microglia plays an important role in the process of neurodegeneration. In this study, we chose retinal detachment as the model of photoreceptor degeneration. We found Myosin 1f was upregulated after retinal detachment, and it was specifically expressed in microglia. Deficiency of myosin 1f protected against photoreceptor apoptosis by inhibiting microglia activation. The elimination of microglia can abolish the protective effect of myosin 1f deficiency. After stimulation by LPS, microglia with myosin 1f deficiency showed downregulation of the MAPK and AKT pathways. Our results demonstrated that myosin 1f plays a crucial role in microglia-induced neuroinflammation after retinal injury and photoreceptor degeneration by regulating two classic inflammatory pathways and thereby decreasing the expression of inflammatory cytokines. Knockout of myosin 1f reduces the intensity of the immune response and prevents cell death of photoreceptor, suggesting that myosin 1f can be inhibited to prevent a decline in visual acuity after retinal detachment.

Myosin 1f-mediated activation of microglia contributes to the photoreceptor degeneration in a mouse model of retinal detachment.

 There have been reports of unexplained visual loss following intra-ocular silicone oil (SiO) tamponade in retinal detachment patients, yet the underlying mechanism is unknown. The aim of this study was to investigate the mechanisms behind retinal toxicity following intra-ocular SiO tamponade in retinal detachment patients.  Vitreous fluid samples were acquired from 27 patients (27 eyes). Twelve eyes for data-independent acquisition (DIA) were divided into four groups: pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RD group), SiO removal after successful retinal reattachment (SO group), cataract surgery after successful retinal reattachment with sterilized air tamponade (FA group), and PPV for epiretinal membrane (ERM group). The remaining 15 eyes were used for enzyme-linked immunosorbent assay analysis. DIA was combined with two-dimensional liquid chromatography-tandem mass spectrometry to find expression changes in the proteome of vitreous. Mean number mass spectra, statistically differentially expressed proteins, gene ontology (GO), pathway representations, and protein interactions were analyzed. GO analysis showed that the protein categories of synapse organization, cell adhesion, and regulation of cell migration in the SO group were differentially expressed compared to the control or FA groups ( < 0.05). Through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, lysosome and cell adhesion were found to be significantly enriched in the SO group compared to the FA and control groups ( < 0.05). Cadherin 2, transferrin, and lysosome function may partially contribute to silicone oil-related vision loss.  Vision loss-inducing novel molecular signatures and pathways that may be associated with SiO toxicity were identified. Transferrin may be a potential visual outcome biomarker for SiO tamponade.

DIA Comparative Proteomic Analysis of Retro-oil Fluid and Vitreous Fluid From Retinal Detachment Patients.

To evaluate the safety, tolerability, and efficacy of efdamrofusp alfa in patients with neovascular age-related macular degeneration (nAMD).

A Novel Bispecific Fusion Protein Targeting C3b/C4b and VEGF in Patients With nAMD: A Randomized, Open-Label, Phase 1b Study.

To determine the predictive value of quantitative morphological parameters for pigment epithelial detachment (PED) of neovascular age-related macular degeneration (nAMD) patients.

Predictive value of pigment epithelial detachment markers for visual acuity outcomes in neovascular age-related macular degeneration.

To identify the disease-causing gene in a Chinese family affected with congenital aniridia.

A novel microdeletion of 517 kb downstream of the PAX6 gene in a Chinese family with congenital aniridia.

Bacoside A (gypenoside, Gyp) is a potent bioactive compound derived from Gynostemma pentaphyllum, known to exert inhibitory effects on various malignant tumors. However, the effects of Gyp on glioma as well as the underlying mechanisms remain unclear. In the present study, we first conducted a comprehensive investigation into the anti-glioma potential of gypenosides using network pharmacology to identify potential glioma-related targets. Protein-protein interaction networks were assembled, and GO and KEGG enrichment analyses were performed for shared targets. Experimental validation involved assessing the viability of U251 and U87 cell lines using the MTS method. Furthermore, trans-well and scratch migration assays evaluated the cell migration, while flow cytometry and Hoechst 33342 staining were utilized for apoptosis assessment. The study also monitored changes in autophagy flow through fluorescence microscopy. The expression levels of proteins pertinent to migration, apoptosis, and autophagy were tested using Western blotting. Findings revealed that Gyp upregulated apoptosis-related proteins (Bax and cleaved caspase-9), downregulated anti-apoptotic protein Bcl-2, and migration-associated matrix metalloproteinases (MMP-2 and MMP-9). Furthermore, autophagy-related proteins (Beclin1 and LC3 II) were upregulated, and p62 protein expression was downregulated. Gyp displayed considerable potential in suppressing glioma progression by inhibiting cell proliferation, invasion, and migration and promoting apoptosis and autophagy. Gyp may offer potential clinical therapeutic choices in glioma management.

Article	Year
A2E Suppresses Regulatory Function of RPE Cells in Th1 Cell Differentiation Via Production of IL-1β and Inhibition of PGE2. Investigative ophthalmology & visual science\| PubMed ID: 26641550	2015
Joint Antiangiogenic Effect of ATN-161 and Anti-VEGF Antibody in a Rat Model of Early Wet Age-Related Macular Degeneration. Molecular pharmaceutics\| PubMed ID: 27089240	2016
The role of N-glycosylation in high glucose-induced upregulation of intercellular adhesion molecule-1 on bovine retinal endothelial cells. Acta ophthalmologica\| PubMed ID: 27151646	2016
Development of a new valid and reliable microsurgical skill assessment scale for ophthalmology residents. BMC ophthalmology\| PubMed ID: 29506509	2018
Comparison of fundus changes following silicone oil and sterilized air tamponade for macular-on retinal detachment patients. BMC ophthalmology\| PubMed ID: 32571251	2020
Peripapillary Vessel Density in Eyes with Rhegmatogenous Retinal Detachment after Pars Plana Vitrectomy. Journal of ophthalmology\| PubMed ID: 33859835	2021
Myosin 1f-mediated activation of microglia contributes to the photoreceptor degeneration in a mouse model of retinal detachment. Cell death & disease\| PubMed ID: 34628463	2021
DIA Comparative Proteomic Analysis of Retro-oil Fluid and Vitreous Fluid From Retinal Detachment Patients. Frontiers in molecular biosciences\| PubMed ID: 34926578	2021
A Novel Bispecific Fusion Protein Targeting C3b/C4b and VEGF in Patients With nAMD: A Randomized, Open-Label, Phase 1b Study. American journal of ophthalmology\| PubMed ID: 36410472	2023
Predictive value of pigment epithelial detachment markers for visual acuity outcomes in neovascular age-related macular degeneration. BMC ophthalmology\| PubMed ID: 36869310	2023
A novel microdeletion of 517 kb downstream of the PAX6 gene in a Chinese family with congenital aniridia. BMC ophthalmology\| PubMed ID: 37752489	2023
Bacoside a inhibits the growth of glioma by promoting apoptosis and autophagy in U251 and U87 cells. Naunyn-Schmiedeberg's archives of pharmacology\| PubMed ID: 37782380	2023

Haiyun Liu

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