MiR-99a-5p Inhibits the Proliferation and Migration of Human Retinal Microvascular Endothelial Cells by Targeting NOX4.

Diabetic retinopathy is one of the common microvascular complications of diabetes, and it is the main cause of vision loss among working-age people. This study interpreted the roles of miR-99a-5p in DR patients and human retinal microvascular endothelial cell (hRMECs) injury induced by high glucose. The expression of miR-99a-5p was detected in patients with NDR, NPDR, and PDR. The indictive impacts of miR-99a-5p were tested by the ROC curve, and the link between miR-99a-5p and clinical information was verified by the Pearson test. HG was used to instruct cell models. The CCK-8 and transwell methods were performed to detect the proliferative and migrated cells. The targeted relationship was explained by luciferase activity. The content of miR-99a-5p was gradually lessened in NPDR and PDR patients. MiR-99a-5p might differentiate DR patients from NDR patients and PDR patients from NPDR patients. The interconnection between miR-99a-5p and clinical factors was endorsed in all DR patients. Overexpression of miR-99a-5p assuaged the abnormality of cell migration and proliferation of hRMECs triggered by HG. NOX4 was a downstream signaling component of miR-99a-5p. In conclusion, MiR-99a-5p protected hRMECs against HG damage, and the miR-99a-5p might be a novel target for diagnosis of DR.

Upregulation of PCED1B-AS1 in proliferative diabetic retinopathy and its involvement in retinal vascular endothelial cell proliferation.

BACKGROUND: This study was to assess the diagnostic value of PCED1B-AS1 for proliferative diabetic retinopathy (PDR) and investigate the involvement of PCED1B-AS1 in PDR. METHODS: The vitreous and blood specimens from 37 subjects with PDR and 21 non-diabetics were examined by reverse transcription quantitative PCR to determine the PCED1B-AS1 level. The two groups were age- and gender-matched. Receiver operating characteristic (ROC) curves were plotted to visually illustrate the diagnostic ability of PCED1B-AS1. Human retinal Müller glial cells were studied by ELISA. Proliferation and migration of human retinal microvascular endothelial cells (HRMECs) were assessed in vitro. RESULTS: Significant increases of PCED1B-AS1 levels were observed in the vitreous samples and CD34 + VEGFR-2 + cells from blood samples of diabetic subjects with PDR, compared with those of non-diabetics. The ROC curve based on the vitreous PCED1B-AS1 levels revealed an AUC of 0.812, while the ROC curve based on the PCED1B-AS1 levels in CD34 + VEGFR-2 + cells from blood samples revealed an AUC of 0.870. In Müller cell cultures, PCED1B-AS1 siRNA significantly attenuated VEGF and MCP-1 upregulation which were induced by CoCl2 and TNF-α. Additionally, PCED1B-AS1 siRNA attenuated VEGF-induced proliferation and migration in HRMECs. CONCLUSION: This study revealed the potential of PCED1B-AS1 as a diagnostic biomarker for PDR. In vitro data point to the anti-angiogenic and anti-proliferation effects of PCED1B-AS1.

Silencing LncRNA PVT1 Reverses High Glucose-Induced Regulation of the High Expression of PVT1 in HRMECs by Targeting miR-128-3p.

This paper aims to discuss the possibility of lncRNA PVT1 as a diagnostic biomarker for diabetic retinopathy (DR) and explore the underlying mechanism. Real-time quantitative polymerase chain reaction (RT-qPCR) was selected to determine the expression level of lncRNA PVT1 in the serum of all subjects. The receiver operating characteristic (ROC) curve reflected the diagnostic significance of PVT1 for DR patients. The Cell Counting Kit-8 (CCK-8) and Transwell assays were used to evaluate the effect of PVT1 expression on the proliferation and migration of human retinal microvascular endothelial cells (HRMECs). The luciferase reporter gene was selected to verify the interaction between PVT1 and miR-128-3p. The relative expression level of PVT1 in serum was higher in both the DB and DR group than in the healthy controls group (HC), and it was highest in the DR group. ROC curve indicated that serum PVT1 could distinguish between HC and DB patients, DB patients and DR patients, respectively. In vitro, high glucose induction significantly increased the proliferation and migration capabilities of HRMECs, but silencing PVT1 (si-PVT1) downregulated the proliferation and migration capabilities of HRMECs. The detection of luciferase reporter gene showed that lncRNA PVT1 targeted miR-128-3p, and there was a negative correlation in the serum of DR patients. In conclusion, this study confirmed that lncRNA PVT1 might regulate the process of DR by targeting miR-128-3p, and has the potential as a biomarker for the diagnosis of DR.

First Human Results With the 256 Channel Intelligent Micro Implant Eye (IMIE 256).

Purpose: To report on the safety and efficacy of the 256-channel Intelligent Micro Implant Eye epiretinal prosthesis system (IMIE 256). Methods: The IMIE 256 implants were implanted in the right eyes of five subjects with end-stage retinitis pigmentosa. Following implantation, the subjects underwent visual rehabilitation training for 90 days, and their visual performance was evaluated using the grating visual acuity test, Tumbling E visual acuity test, direction of motion, square localization, and orientation and mobility test. To evaluate the safety of the IMIE 256, all adverse events were recorded. Results: Subjects performed significantly better on all evaluations with the IMIE 256 system on as compared with the performance at baseline or with the system off. There was a steady improvement in performance at each observation interval, indicating that the training and/or practice helped the subjects use the IMIE 256. There were two serious adverse events-electrode array movement and low intraocular pressure in one subject, which resolved with surgery. There were no other adverse events observed except those expected in the course of postoperative healing. Conclusions: These results show an improved safety and efficacy profile compared with that of the Argus II implant. Further clinical trials are needed to confirm these results in a larger number of subjects and over longer durations. Translational Relevance: To our knowledge, this study reports the first in-human data from a high-density (256 electrodes) epiretinal implant to restore sight to a subset of blind patients.