RNA-binding proteins potentially regulate the alternative splicing of cell cycle-associated genes in proliferative diabetic retinopathy.

RNA-binding proteins (RBPs) contribute to the pathogenesis of proliferative diabetic retinopathy (PDR) by regulating gene expression through alternative splicing events (ASEs). However, the RBPs differentially expressed in PDR and the underlying mechanisms remain unclear. Thus, this study aimed to identify the differentially expressed genes in the neovascular membranes (NVM) and retinas of patients with PDR. The public transcriptome dataset GSE102485 was downloaded from the Gene Expression Omnibus database, and samples of PDR and normal retinas were analyzed. A mouse model of oxygen-induced retinopathy was used to confirm the results. The top 20 RBPs were screened for co-expression with alternative splicing genes (ASGs). A total of 403 RBPs were abnormally expressed in the NVM and retina samples. Functional analysis demonstrated that the ASGs were enriched in cell cycle pathways. Cell cycle-associated ASEs and an RBP-AS regulatory network, including 15 RBPs and their regulated ASGs, were extracted. Splicing factor proline/glutamine rich (SFPQ), microtubule-associated protein 1 B (MAP1B), heat-shock protein 90-alpha (HSP90AA1), microtubule-actin crosslinking factor 1 (MACF1), and CyclinH (CCNH) expression remarkably differed in the mouse model. This study provides novel insights into the RBP-AS interaction network in PDR and for developing screening and treatment options to prevent diabetic retinopathy-related blindness.

CREG Protects Retinal Ganglion Cells loss and Retinal Function Impairment Against ischemia-reperfusion Injury in mice via Akt Signaling Pathway.

PURPOSE: The irreversible death of retinal ganglion cells (RGCs) plays an important role in the pathogenesis of glaucoma. Cellular repressor of E1A-stimulated genes (CREG), a secreted glycoprotein involved in cellular proliferation and differentiation, has been shown to protect against myocardial and renal ischemia-reperfusion damage. However, the role of CREG in retinal ischemia-reperfusion injury (RIRI) remains unknown. In this study, we aimed to explore the effect of CREG on RGCs apoptosis after RIRI. METHODS: We used male C57BL/6J mice to establish the RIRI model. Recombinant CREG was injected at 1 day before RIRI. The expression and distribution of CREG were examined by immunofluorescence staining and western blotting. RGCs survival was assessed by immunofluorescence staining of flat-mounted retinas. Retinal apoptosis was measured by the staining of TdT-mediated dUTP nick-end labeling and cleaved caspase-3. Electroretinogram (ERG) analysis and optomotor response were conducted to evaluate retinal function and visual acuity. The expressions of Akt, phospho-Akt (p-Akt), Bax, and Bcl-2 were analyzed by western blotting to determine the signaling pathways of CREG. RESULTS: We found that CREG expression was decreased after RIRI, and intravitreal injection of CREG attenuated RGCs loss and retinal apoptosis. Besides, the amplitudes of a-wave, b-wave, and photopic negative response (PhNR) in ERG, as well as visual function, were significantly restored after treatment with CERG. Furthermore, intravitreal injection of CREG upregulated p-Akt and Bcl-2 expression and downregulated Bax expression. CONCLUSION: Our results demonstrated that CREG protected RGCs from RIRI and alleviated retinal apoptosis by activating Akt signaling. In addition, CREG also improved retinal function and visual acuity.

Application of Platelet-Rich Fibrin Transplantation for Large Macular Hole.

Purpose Large idiopathic macular hole (MH) has a lower closure rate and poor visual prognosis. To increase the closure rate and the visual outcome in patients with large MH, we evaluate a technique of platelet-rich fibrin (PRF) membrane transplantation for the treatment of large MH.Methods This was a prospective interventional study. Seventeen eyes of 17 patients (8 males and 9 females) with large MH (654.94 ± 188.08 µm) underwent pars plana vitrectomy and internal limiting membrane peeling followed by PRF transplantation between January 2019 and December 2020. The patients were followed up for at least 6 months. Preoperatively and postoperatively, all patients underwent comprehensive ophthalmic examinations, including best-corrected visual acuity (BCVA), intraocular pressure, slit-lamp biomicroscopy, indirect ophthalmoscopy, ultra-widefield retinal imaging, optical coherent tomography, and optical coherent tomography angiography.Results All the patients achieved complete and consistent hole closure after the surgery (100%). At 6 months follow-up, the external limiting membrane defects were observed in 3 eyes (17.64%), and the ellipsoid zone defects were observed in 10 eyes (58.82%). The preoperative BCVA was 1.21 ± 0.33 in logMAR. Postoperatively, the BCVA was significantly improved to 0.64 ± 0.22 in logMAR at 6 months (p < 0.001). The foveal avascular zone reduced significantly from 0.41 ± 0.08 mm2 to 0.26 ± 0.07 mm2 (p < 0.001). No complications were observed during or after the operation.Conclusions All patients in this study have achieved good anatomic and functional results, which indicate that the application of PRF transplantation is an effective and safe technique for large MH.

Polyfluorene-based white light conjugated polymers incorporating orange iridium(iii) complexes: the effect of steric configuration on their photophysical and electroluminescent properties.

Different kinds of polyfluorene-based white light conjugated polymers with phosphorescent iridium(iii) complexes as orange emission groups and polyfluorene as blue emission groups were designed and synthesized. On the basis of adjusting substituent positions on iridium(iii) complexes, the conjugated polymers exhibited different steric configurations, i.e. hyperbranched and linear structures, and the PL emission peaks of iridium(iii) complexes had a significant change. Compared to linear conjugated polymers, hyperbranched white light conjugated polymers showed the best thermal stability and film forming properties. The white light single-emissive-layer devices with simplified configuration were also prepared in a wet process. All these devices realized good electroluminescence, especially the hyperbranched conjugated polymers in which the roll off phenomenon at high current density was effectively suppressed. Furthermore, EL spectra of hyperbranched polymers exhibited good stability at different driving voltages. A maximum luminance of 2469 cd m-2, a maximum current efficiency of 1.73 cd A-1 and the commission internationale de l'Eclairage (CIE) coordinates of (0.25, 0.23) showed white light was achieved from the HPF-Ir10 devices.