Activation of the TXNIP/NLRP3 inflammasome pathway contributes to inflammation in diabetic retinopathy: a novel inhibitory effect of minocycline.

OBJECTIVE AND DESIGN: Chronic low-grade inflammation occurs in diabetic retinopathy (DR), but the underlying mechanism(s) remains (remain) unclear. NLRP3 inflammasome activation is involved in several other inflammatory diseases. Thus, we investigated the role of the NLRP3 inflammasome signaling pathway in the pathogenesis of DR. METHODS: Diabetes was induced in rats by streptozotocin treatment for 8 weeks. They were treated with NLRP3 shRNA or minocycline during the last 4 weeks. High glucose-exposed human retinal microvascular endothelial cells (HRMECs) were co-incubated with antioxidants or subjected to TXNIP or NLRP3 shRNA interference. RESULTS: In high glucose-exposed HRMECs and retinas of diabetic rats, mRNA and protein expression of NLRP3, ASC, and proinflammatory cytokines were induced significantly by hyperglycemia. Upregulated interleukin (IL)-1ß maturation, IL-18 secretion, and caspase-1 cleavage were also observed with increased cell apoptosis and retinal vascular permeability, compared with the control group. NLRP3 silencing blocked these effects in the rat model and HRMECs, confirming that inflammasome activation contributed to inflammation in DR. TXNIP expression was increased by reactive oxygen species (ROS) overproduction in animal and cell models, whereas antioxidant addition or TXNIP silencing blocked IL-1ß and IL-18 secretion in high glucose-exposed HRMECs, indicating that the ROS-TXNIP pathway mediates NLRP3 inflammasome activation. Minocycline significantly downregulated ROS generation and reduced TXNIP expression, subsequently inhibited NLRP3 activation, and further decreased inflammatory factors, which were associated with a decrease in retinal vascular permeability and cell apoptosis. CONCLUSIONS: Together, our data suggest that the TXNIP/NLRP3 pathway is a potential therapeutic target for the treatment of DR, and the use of minocycline specifically for such therapy may be a new avenue of investigation in inflammatory disease.

Effect of corneal diameter on preoperative screening results for corneal refractive surgery.

AIMS: To investigate the impact of different corneal diameters on corneal morphology and biomechanical outcome during preoperative screening for corneal refractive surgery. METHODS: A retrospective analysis was conducted on 300 patients who underwent corneal refractive surgery at Eye and ENT Hospital, Fudan University between October 2023 and December 2023. All patients had no history of keratoconus or previous corneal surgery. Patients were categorized into two groups based on corneal topography measurements: (1) normal corneal diameter group (n=159), those with corneal diameter ranging from 11.5 mm to 12.0 mm; (2) abnormal corneal diameter group (n=141), those with corneal diameter smaller than 10.0 mm or larger than 12.5 mm. Corneal thickness, morphologic data, and biomechanical data were measured using Pentacam corneal topography. Correlation analysis was conducted to explore the relationship between corneal diameter and various corneal topography and biomechanical data. RESULTS: Significant differences were observed in corneal topography data including BFSf (F=43.21), BFSb (F=30.24), Df (F=15.32), Dp (F=32.36), Da (F=9.66), D (F=58.36), PPIavg (F=32.64), and ARTmax (F=12.06) between the groups (P<0.05). Additionally, BFSf, BFSb, Db, Dp, D, and PPIavg exhibited statistically significant differences between any two groups (P<0.05). Significant differences were also found in Df, Da, and ARTmax between small and large corneas, as well as between normal-sized and large corneas (P<0.05). Correlation analysis indicated negative correlations between corneal diameter and A1V (r=-0.12), HCdArcLength (r=-0.17), CBI (r=-0.27), bIOP (r=-0.13), Df (r=-0.025), PPIavg (r=-0.028), and TBI (r=-0.27). Conversely, BFSf (r=0.009), BFSb (r=0.001), PD (r=0.15), and ARTH (r=0.37) displayed positive correlations with corneal diameter. CONCLUSIONS: Corneal diameter significantly affects preoperative screening for corneal refractive surgery. Smaller corneal diameters exhibit a greater influence on the corneal topography BAD analysis system.

Corrigendum: Diabetes Onset at 31-45 Years of Age is Associated with an Increased Risk of Diabetic Retinopathy in Type 2 Diabetes.

This corrects the article DOI: 10.1038/srep38113.

Diabetes Onset at 31-45 Years of Age is Associated with an Increased Risk of Diabetic Retinopathy in Type 2 Diabetes.

This hospital-based, cross-sectional study investigated the effect of age of diabetes onset on the development of diabetic retinopathy (DR) among Chinese type 2 diabetes mellitus (DM) patients. A total of 5,214 patients with type 2 DM who were referred to the Department of Ophthalmology at the Shanghai First People's Hospital from 2009 to 2013 was eligible for inclusion. Diabetic retinopathy status was classified using the grading system of the Early Treatment Diabetic Retinopathy Study (ETDRS). Logistic and hierarchical regression analyses were used to identify independent variables affecting the development of DR. Upon multiple logistic regression analysis, patient age at the time of diabetes onset was significantly associated with development of DR. Further, when the risk of retinopathy was stratified by patient age at the onset of diabetes, the risk was highest in patients in whom diabetes developed at an age of 31-45 years (odds ratio [OR] 1.815 [1.139-2.892]; p = 0.012). Furthermore, when patients were divided into four groups based on the duration of diabetes, DR development was maximal at a diabetes onset age of 31-45 years within each group. A diabetes onset age of 31-45 years is an independent risk factor for DR development in Chinese type 2 DM patients.