Corticosteroids have for some time been used as first-line drugs for the topical treatment of noninfectious uveitis, but poor ocular bioavailability and the rapid clearance of eye drops necessitate frequent dosing, reducing patient compliance. In this study, we used an acid-sensitive stearoxyl-ketal-dexamethasone pro-drug microcrystals (SKD MCs), which is consistently safe and effective in the control of uveitis inflammation in rats. We used a rat model of experimental autoimmune uveitis (EAU) to evaluate the effects of SKD MCs in terms of clinical manifestations, molecular biology, pathological histology, and visual electrophysiology compared to dexamethasone sodium phosphate injection or phosphate-buffered saline. SKD MCs significantly reduced inflammation in EAU, improved the ability to suppress inflammatory cytokines and to protect retinal function, and significantly reduced retinal microglia activation, with no increase in intraocular pressure throughout the treatment. Our results indicate that the SKD MCs formulation holds promise as a new strategy for the treatment of noninfectious uveitis and potentially other ocular inflammatory diseases.

Background: Arginase-1 (ARG1) promotes collagen synthesis and cell proliferation. ARG1 is highly expressed in various tumour cells. The mechanisms of ARG1 in epithelial-to-mesenchymal transition (EMT)-associated cataracts were studied herein. Methods: C57BL/6 mice, a human lens epithelial cell line (HLEC-SRA01/04), and human lens capsule samples were used in this study. The right lens anterior capsule of the mouse eye was punctured through the central cornea with a 26-gauge hypodermic needle. Human lens epithelial cells (HLECs) were transfected with ARG1-targeted (siARG1) or negative control siRNA (siNC). For gene overexpression, HLECs were transfected with a plasmid bearing the ARG1 coding sequence or an empty vector. Medium containing 0.2% serum with or without transforming growth factor beta-2 (TGF-β2) was added for 6 or 24 h to detect mRNA or protein, respectively. The expression of related genes was measured by quantitative real-time polymerase chain reaction (RT–qPCR), western blotting, and immunohistochemical staining. Transwell assays and wound healing assays were used to determine cell migration. Cell proliferation, superoxide levels, nitric oxide (NO) levels, and arginase activity were estimated using Cell Counting Kit-8 assays, a superoxide assay kit, an NO assay kit, and an arginase activity kit. Results: ARG1, alpha-smooth muscle actin (α-SMA), fibronectin, and Ki67 expression increased after lens capsular injury, while zonula occludens-1 (ZO-1) expression decreased. Fibronectin and collagen type I alpha1 chain (collagen 1A1) expression increased, and cell migration increased significantly in ARG1-overexpressing HLECs compared with those transfected with an empty vector after TGF-β2 treatment. These effects were reversed by ARG1 knockdown. The arginase-related pathway plays an important role in EMT. mRNAs of enzymes of the arginase-related pathway were highly expressed after ARG1 overexpression. ARG1 knockdown suppressed these expression changes. Numidargistat (CB-1158) dihydrochloride (CB-1158), an ARG1 inhibitor, suppressed TGF-β2-induced anterior subcapsular cataract (ASC) by reducing the proliferation of lens epithelial cells (LECs) and decreasing fibronectin, α-SMA, collagen 1A1, and vimentin expression. Compared with that in nonanterior subcapsular cataract (non-ASC) patients, the expression of ARG1, collagen 1A1, vimentin, fibronectin, and Ki67 was markedly increased in ASC patients. Conclusions: ARG1 can regulate EMT in EMT-associated cataracts. Based on the pathogenesis of ASC, these findings are expected to provide new therapeutic strategies for patients. Graphical

The recent advancement in the management of chronic renal failure (CRF) has significantly increased the longevity of the patients, which increase the incidence of severe vitreoretinopathy. The vitrectomy is highly risky in this particular group of patients due to their systemic comorbidity. The timing surgical intervention is usually delayed because of the systemic conditions. This study is to evaluate the safety and effectiveness of 25-guage vitrectomy for severe vitreoretinopathy in the CRF patients. In this retrospective study, 16 eyes of 16 CRF patients with severe vitreoretinopathy were undergone 25-guage vitrectomy in the department of Ophthalmology of the Second Hospital of Tianjin Medical University from February 2015 to April 2017. The visual outcome, complications and perioperative medical management were documented and analyzed. The best-corrected visual acuity(BCVA)of fourteen eyes were lower than 20/200 preoperatively. Surgery duration ranged from 28 to 72 min, with a mean of 48.4 ± 13.6 min. During the surgery, 12 eyes were diagnosed with DR, while two them were complicated with tractional retinal detachment and one with branch retinal vein occlusion. Three eyes were diagnosed with branch retinal vein occlusion, and one eye was diagnosed with hypertensive retinopathy. Postoperative BCVA of six eyes ≥20/40, seven eyes ≥20/200, and three eyes < 20/200. BCVA of eight eyes improved more than three lines, three eyes improved two lines, and four eyes improved one line. BCVA decreased from hand movement to light perception in one patient who developed neovascular glaucoma two weeks after surgery. In chronic renal failure patients with severe vitreoretinopathy, the well-planned minimally invasive vitrectomy is effective and safe. Additionally, careful management of the perioperative systemic conditions is important to improve the visual acuity and quality of life as well.