Dr. Yang obtained doctorate degree in Ophthalmology at 2017 in Tongji University, Shanghai, China. Afterwards, He works as an eye doctor in Shanghai Tenth People's Hospital. His clinial and experimantal interest is retinal disease. In June 2023, he joined Prof. Hartnett's lab to conduct postdoctoral research in neovascularization-related retinal diseases.
Mary Elizabeth Hartnett, Postdoctoral Faculty Sponsor
TSPAN4-positive migrasome derived from retinal pigmented epithelium cells contributes to the development of proliferative vitreoretinopathy
JOURNAL OF NANOBIOTECHNOLOGY
2022; 20 (1): 519
Proliferative vitreoretinopathy (PVR) is a blind-causing disease initiated by the activation of retinal pigmented epithelium (RPE) primarily induced by TGF-β families. Migrasome is a recently discovered type of extracellular vesicle related to cell migration.Here, we used ex vivo, in vitro, and in vivo models, to investigate the characteristics and functions of migrasomes in RPE activation and PVR development. Results indicated that the migrasome marker tetraspanin-4 (TSPAN4) was abundantly expressed in human PVR-associated clinical samples. The ex vivo model PVR microenvironment is simulated by incubating brown Norway rat RPE eyecups with TGF-β1. Electron microscope images showed the formation of migrasome-like vesicles during the activation of RPE. Further studies indicated TGF-β1 increased the expression of TSPAN4 which results in migrasome production. Migrasomes can be internalized by RPE and increase the migration and proliferation ability of RPE. Moreover, TSPAN4-inhibited RPE cells are with reduced ability of initiating experimental PVR. Mechanically, TSPAN4 expression and migrasome production are induced through TGF-β1/Smad2/3 signaling pathway.In conclusion, migrasomes can be produced by RPE under PVR microenvironment. Migrasomes play a pivotal role in RPE activation and PVR progression. Thus, targeting TSPAN4 or blocking migrasome formation might be a new therapeutic method against PVR.
View details for DOI 10.1186/s12951-022-01732-y
View details for Web of Science ID 000896639200003
View details for PubMedID 36494806
View details for PubMedCentralID PMC9733225
Long noncoding RNA ERLR mediates epithelial-mesenchymal transition of retinal pigment epithelial cells and promotes experimental proliferative vitreoretinopathy
CELL DEATH AND DIFFERENTIATION
2021; 28 (8): 2351-2366
Proliferative vitreoretinopathy (PVR) is a disease that causes severe blindness and is characterized by the formation of contractile fibrotic subretinal or epiretinal membranes. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a hallmark of PVR. This work aims to examine the role of a long noncoding RNA (lncRNA) named EMT-related lncRNA in RPE (ERLR, LINC01705-201 (ENST00000438158.1)) in PVR and to explore the underlying mechanisms. In this study, we found that ERLR is upregulated in RPE cells stimulated with transforming growth factor (TGF)-β1 as detected by lncRNA microarray and RT-PCR. Further studies characterized full-length ERLR and confirmed that it is mainly expressed in the cytoplasm. In vitro, silencing ERLR in RPE cells attenuated TGF-β1-induced EMT, whereas overexpressing ERLR directly triggered EMT in RPE cells. In vivo, inhibiting ERLR in RPE cells reduced the ability of cells to induce experimental PVR. Mechanistically, chromatin immunoprecipitation (ChIP) assays indicated that the transcription factor TCF4 directly binds to the promoter region of ERLR and promotes its transcription. ERLR mediates EMT by directly binding to MYH9 protein and increasing its stability. TCF4 and MYH9 also mediate TGF-β1-induced EMT in RPE cells. Furthermore, ERLR is also significantly increased in RPE cells incubated with vitreous PVR samples. In clinical samples of PVR membranes, ERLR was detected through fluorescent in situ hybridization (FISH) and colocalized with the RPE marker pancytokeratin (pan-CK). These results indicated that lncRNA ERLR is involved in TGF-β1-induced EMT of human RPE cells and that it is involved in PVR. This finding provides new insights into the mechanism and treatment of PVR.
View details for DOI 10.1038/s41418-021-00756-5
View details for Web of Science ID 000625831100002
View details for PubMedID 33664479
View details for PubMedCentralID PMC8329214
The Interplay Between E-Cadherin, Connexin 43, and Zona Occludens 1 in Retinal Pigment Epithelial Cells
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
2019; 60 (15): 5104-5111
Cell-cell contact in retinal pigment epithelium (RPE) involves adherent junctions, gap junctions, and tight junctions, which are primarily composed by E-cadherin, zona occludens 1 (ZO-1), and connexin 43, respectively. Here, we aimed to explore the relationship and interplay between these junction-associated proteins.E-cadherin, connexin 43, and ZO-1 expression in human primary RPE in the early phase after TGF-β1 stimulation was detected. The knockdown of E-cadherin, ZO-1, and connexin 43 was performed to characterize the regulatory network involving these three proteins. Dye transfer and FITC-dextran permeability assays were conducted to observe the epithelial functional alterations. Transmission electron microscopy (TEM) was used to observe the ultrastructure of the cell-cell junctions in mouse RPE. The immunofluorescence staining and coimmunoprecipitation were performed to observe the colocalization and the physical association of E-cadherin, ZO-1, and connexin 43.Among these three components, E-cadherin appeared to be the first protein that was downregulated after TGF-β1 treatment. The ultrastructures of adherent junctions, gap junctions, and tight junctions could be observed in mouse RPE by TEM. E-cadherin, ZO-1, and connexin 43 were colocalized and physically bound to each other. The knockdown of one of these three proteins led to downregulation of the other two proteins and compromised epithelial function.E-cadherin, ZO-1, and connexin 43 were physically associated with each other and were mutually regulated. To enhance the understanding of cell-cell contacts, a holistic view is needed. Our results provide new insights in RPE disorders such as proliferative vitreoretinopathy.
View details for DOI 10.1167/iovs.19-27768
View details for Web of Science ID 000507640100017
View details for PubMedID 31826237
Optical coherence tomography angiography characteristics of acute retinal arterial occlusion
2019; 19: 147
To characterize the vascular changes in eyes within the acute phase of retinal arterial occlusion (RAO) by optical coherence tomography angiography (OCT-A) imaging.This was a retrospective, observational study. Nineteen patients with RAO (symptom onset within 7 days) and 19 age and sex-matched normal control individuals were included. A comprehensive ophthalmic examination and OCT-A examination were conducted for all the patients.The vessel density of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and area with a width of 300 μm around the FAZ (FD-300) was significantly reduced in RAO patients compared with that in the fellow eyes and normal control eyes. The vessel density of the SCP of RAO fellow eyes was significantly lower than that of the normal control eyes (all P < 0.05). Though no difference was observed in the FAZ of RAO eyes compared with that of fellow eyes and normal control eyes, the acircularity index (AI) of the FAZ was significantly increased in RAO eyes (P < 0.05). Central macular thickness (CMT) was correlated with best-corrected visual acuity in central retinal arterial occlusion (CRAO) patients (r = 0.626, P = 0.024). In BRAO eyes, the vessel density of the RAO-affected hemifield was significantly reduced compared with that of the unaffected hemifield (P < 0.05). Radial peripapillary plexus (RPC) vessel density was reduced, accompanied by retinal nerve fiber layer (RNFL) thinning in 3 available CRAO patients.As a valuable noninvasive imaging tool, OCT-A provides deeper and more detailed vascular information that extends our understanding of the vasculature alterations in acute RAO.
View details for DOI 10.1186/s12886-019-1152-8
View details for Web of Science ID 000475739700002
View details for PubMedID 31291918
View details for PubMedCentralID PMC6621973