Decreasing mitochondrial fission ameliorates HIF-1α-dependent pathological retinal angiogenesis.

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.

Prediction of allograft function in pre-transplant kidneys using sound touch elastography (STE): an ex vivo study.

BACKGROUND: The purpose of the study was to evaluate renal quality and predict posttransplant graft function using ex vivo sound touch elastography (STE). METHODS: In this prospective study, 106 donor kidneys underwent ex vivo STE examination and biopsy from March 2022 to August 2023. The mean stiffness of the superficial cortex (STEsc), deep cortex (STEdc), and medulla (STEme) was obtained and synthesized into one index (STE) through the factor analysis method. Additionally, 100 recipients were followed up for 6 months. A random forest algorithm was employed to explore significant predictive factors associated with the Remuzzi score and allograft function. The performance of parameters was evaluated by using the area under the receiver operating characteristic curve (AUC). RESULTS: STE had AUC values of 0.803 for diagnosing low Remuzzi and 0.943 for diagnosing high Remuzzi. Meanwhile, STE had an AUC of 0.723 for diagnosing moderate to severe ATI. Random forest algorithm identified STE and Remuzzi score as significant predictors for 6-month renal function. The AUC for STE in predicting postoperative allograft function was 0.717, which was comparable with that of the Remuzzi score (AUC = 0.756). Nevertheless, the specificity of STE was significantly higher than that of Remuzzi (0.913 vs 0.652, p < 0.001). Given these promising results, donor kidneys can be transplanted directly without the need for biopsy when STE ≤ 11.741. CONCLUSIONS: The assessment of kidney quality using ex vivo STE demonstrated significant predictive value for the Remuzzi score and allograft function, which could help avoid unnecessary biopsy. CRITICAL RELEVANCE STATEMENT: Pre-transplant kidney quality measured with ex vivo STE can be used to assess donor kidney quality and avoid unnecessary biopsy. KEY POINTS: STE has significant value for diagnosing low Remuzzi and high Remuzzi scores. STE achieved good performance in predicting posttransplant allograft function. Assessment of kidney quality using ex vivo STE could avoid unnecessary biopsies.

[Mechanism of keratinocyte growth factor-2 accelerating corneal epithelial wound healing on rabbit alkali burned cornea].

OBJECTIVE: To evaluate the curative effect of KGF-2 on the alkali-injured rabbit eye and to investigate the mechanism of KGF-2 accelerating corneal epithelial wound healing. METHODS: Alkali burn was produced in 24 corneas from 24 New Zealand rabbits. Four groups were randomly divided. Three groups (A, B, and C groups) were treated with KGF-2 solution (1, 50, 100 microg/ml, respectively), and one group (D group) was treated with phosphate-buffered saline (PBS) solution. The injured eyes were photographed after the fluorescence staining with a slit lamp and the pictures were analyzed with computer-aided picture analysis system to calculate the rate of corneal epithelial healing. Morphologic and immunohistological examinations (using P63, AE5 and EGFR antibodies) of the cornea were performed. RESULTS: KGF-2 at dosages ranging from 1 microg/ml to 100 microg/ml could enhance the cornea wound healing process. After 24 hours, epithelial healing rate of the 100 microg/ml KGF-2 group and the PBS treated group was 74% and 40%, respectively (P < 0.05). The corneal epithelial healing rate of each group was variable after four days and achieved complete healing after ten days. The P63 positive cells in KGF-2 groups appeared not only in the limbal area but also in the central area. For example, on the seventh day, in the limbal area, the P63 positive cells in the 100 microg/ml KGF-2 group, the PBS treated group and the normal group were 53.8 +/- 2.6, 29.5 +/- 2.2 and 17.0 +/- 2.1, respectively (P = 0.000). At the same time, the P63 positive cells in the non-limbal area in the 100 microg/ml KGF-2 group, the PBS treated group and the normal group were 69.5 +/- 2.8, 19.5 +/- 2.8 and 0, respectively (P = 0.000). CONCLUSIONS: These results suggested KGF-2 can stimulate the limbal epithelial stem cells to migrate to the central cornea. KGF-2 can accelerate the healing of alkali burned cornea.