Knockdown of ChREBP ameliorates retinal microvascular endothelial cell injury and angiogenic responses in diabetic retinopathy.

PURPOSE: To examine whether and how carbohydrate response element-binding protein (ChREBP) plays a role in diabetic retinopathy. METHODS: Western blotting was used to detect ChREBP expression and location following high glucose stimulation of Human Retinal Microvascular Endothelial Cells (HRMECs). Flow cytometry, TUNEL staining, and western blotting were used to evaluate apoptosis following ChREBP siRNA silencing. Cell scratch, transwell migration, and tube formation assays were used to determine cell migration and angiogenesis. Diabetic models for wild-type (WT) and ChREBP knockout (ChKO) mice were developed. Retinas of WT and ChKO animals were cultivated in vitro with vascular endothelial growth factor + high glucose to assess neovascular development. RESULTS: ChREBP gene knockdown inhibited thioredoxin-interacting protein and NOD-like receptor family pyrin domain containing protein 3 expression in HRMECs, which was caused by high glucose stimulation, reduced apoptosis, hindered migration, and tube formation, and repressed AKT/mTOR signaling pathway activation. Compared with WT mice, ChKO mice showed suppressed high glucose-induced alterations in retinal structure, alleviated retinal vascular leakage, and reduced retinal neovascularization. CONCLUSIONS: ChREBP deficiency decreased high glucose-induced apoptosis, migration, and tube formation in HRMECs as well as structural and angiogenic responses in the mouse retina; thus, it is a potential therapeutic target for diabetic retinopathy.

PI3K/AKT/mTOR pathway-derived risk score exhibits correlation with immune infiltration in uveal melanoma patients.

Uveal melanoma (UVM) is a rare but highly aggressive intraocular tumor with a poor prognosis and limited therapeutic options. Recent studies have implicated the PI3K/AKT/mTOR pathway in the pathogenesis and progression of UVM. Here, we aimed to explore the potential mechanism of PI3K/AKT/mTOR pathway-related genes (PRGs) in UVM and develop a novel prognostic-related risk model. Using unsupervised clustering on 14 PRGs profiles, we identified three distinct subtypes with varying immune characteristics. Subtype A demonstrated the worst overall survival and showed higher expression of human leukocyte antigen, immune checkpoints, and immune cell infiltration. Further enrichment analysis revealed that subtype A mainly functioned in inflammatory response, apoptosis, angiogenesis, and the PI3K/AKT/mTOR signaling pathway. Differential analysis between different subtypes identified 56 differentially expressed genes (DEGs), with the major enrichment pathway of these DEGs associated with PI3K/AKT/mTOR. Based on these DEGs, we developed a consensus machine learning-derived signature (RSF model) that exhibited the best power for predicting prognosis among 76 algorithm combinations. The novel signature demonstrated excellent robustness and predictive ability for the overall survival of patients. Moreover, we observed that patients classified by risk scores had distinguishable immune status and mutation. In conclusion, our study identified a consensus machine learning-derived signature as a potential biomarker for prognostic prediction in UVM patients. Our findings suggest that this signature is correlated with tumor immune infiltration and may serve as a valuable tool for personalized therapy in the clinical setting.

Structural and functional retinal changes in patients with type 2 diabetes without diabetic retinopathy.

OBJECTIVE: The characteristics of the early changes in preclinical diabetic retinopathy (DR) are poorly known. This study aimed to analyse the changes in the structure and function of the fundus in diabetic patients without diabetic retinopathy (NDR). METHODS: This prospective study enrolled patients with type 2 diabetes and healthy controls from April to December 2020. Retinal sensitivity was measured by microperimetry. The peripapillary retinal nerve fibre layer (p-RNFL) thickness, macular retinal thickness, and retinal volume were measured by optical coherence tomography (OCT). The vessel density (VD) and perfusion density (PD) of the peripapillary area, as well as the foveal avascular zone (FAZ) area, FAZ perimeter, and FAZ circularity, were measured by optical coherence tomographic angiography (OCTA). RESULTS: A total of 71 cases (100 eyes) were enrolled in the study, including 34 cases (51 eyes) in the NDR group and 37 cases (49 eyes) in the control group. The mean retinal sensitivity was lower in the NDR group than in the control group for all sectors (all p < .001). Compared with controls, the NDR group showed thinner p-RNFL in the T sector (76.24 ± 14.29 vs. 85.47 ± 19.66 µm, p = .035). The NDR group had a thinner retina in the N2 sector (304.55 ± 16.07 vs. 312.02 ± 12.30 µm, p = .010). The PD of DCP was lower in the N2 sector in the NDR group (44.92 ± 11.77 vs. 50.27 ± 6.37%, p = .044). The VD was higher in the NDR group in RPCP-S/N/I, and the PD was higher in the RPCP-S/N (all p < .05). The frequencies of perifoveal capillary drop-out, notched or punched out borders of the superficial FAZ, and loss of smooth contour were all higher in the NDR group (all p < .05). CONCLUSION: The structure (p-RNFL thickness, VD, and PD) and function (retinal sensitivity) display some changes in diabetic patients even if they had not been found to have DR.Key messagesDecreased retinal sensitivity was observed in diabetic patients before the onset of diabetic retinopathy.Compared with the control group, we found the changes in vessel density or perfusion density in a certain area, whether in SCP, DCP, or RPCP in the NDR group.Before the onset of diabetic retinopathy, the structure and function of the retina in diabetic patients had changed.

Multimodal Imaging of Parry Romberg Syndrome-associated Panuveitis: A Case Report and Review of Literature.

Purpose: We describe a case of Parry-Romberg syndrome (PRS) presenting with panuveitis and retinal vasculitis.Methods: We conducted a retrospective review of our patient's case and related literature published through May 2019.Results: A 26-year-old woman with history of PRS was diagnosed with panuveitis and retinal vasculitis. Intraocular inflammation was controlled with local and systemic corticosteroids. The relationship between PRS and intraocular inflammation is discussed with references to the relevant on literature.Conclusions: Our findings and the accompanying literature review suggest that the patient's ocular involvement included multiple fundus lesions, retinal vascular disorder, and unilateral poliosis - all of which may be attribute to trigeminal neuro vasculitis. As the Varicella-zoster virus may contribute to the onset of the autoimmune processes associated with PRS, this requires further exploration. This report confirms the utility of multimodal imaging in the study, screening, and follow-up of intraocular inflammation in patients with PRS.