Glaucoma can result in retinal ganglion cell (RGC) death and permanently damaged vision. Pathologically high intraocular pressure (ph-IOP) is the leading cause of damaged vision during glaucoma; however, controlling ph-IOP alone does not entirely prevent the loss of glaucomatous RGCs, and the underlying mechanism remains elusive. In this study, we reported an increase in ferric iron in patients with acute primary angle-closure glaucoma (the most typical glaucoma with ph-IOP damage) compared with the average population by analyzing free iron levels in peripheral serum. Thus, iron metabolism might be involved in regulating the injury of RGCs under ph-IOP. In vitro and in vivo studies confirmed that ph-IOP led to abnormal accumulation of ferrous iron in cells and retinas at 1–8 h post-injury and elevation of ferric iron in serum at 8 h post-injury. Nuclear receptor coactivator 4 (NCOA4)-mediated degradation of ferritin heavy polypeptide 1(FTH1) is essential to disrupt iron metabolism in the retina after ph-IOP injury. Furthermore, knockdown of Ncoa4 in vivo inhibited FTH1 degradation and reduced the retinal ferrous iron level. Elevated ferrous iron induced by ph-IOP led to a marked accumulation of pro-ferroptotic factors (lipid peroxidation and acyl CoA synthetase long-chain family member 4) and a depletion of anti-ferroptotic factors (glutathione, glutathione peroxidase 4, and nicotinamide adenine dinucleotide phosphate). These biochemical changes resulted in RGC ferroptosis. Deferiprone can pass through the blood-retinal barrier after oral administration and chelated abnormally elevated ferrous iron in the retina after ph-IOP injury, thus inhibiting RGC ferroptosis and protecting visual function. In conclusion, this study revealed the role of NCOA4-FTH1-mediated disturbance of iron metabolism and ferroptosis in RGCs during glaucoma. We demonstrate the protective effect of Deferiprone on RGCs via inhibition of ferroptosis, providing a research direction to understand and treat glaucoma via the iron homeostasis and ferroptosis pathways.

Retinoblastoma (RB) is a common neoplasm that is exhibited in individuals globally. Increasing evidence demonstrated that cyclin-dependent kinase regulatory subunit 1B (CKS1B) may be involved in the pathogenesis of various tumor types, including multiple myeloma and breast cancer. In the present study, the hypothesis that CKS1B down-regulation would effectively inhibit the proliferation, invasion and angiogenesis of RB cells through the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway was examined. Initial investigation of the expression profile of CKS1B in RB and adjacent retina tissues was performed using reverse transcription-quantitative polymerase chain reaction and western blot analysis. A total of three RB cell lines, SO-RB50, Y79 and HXO-RB44, were examined for selection of the cell line with the highest expression of CKS1B, and human normal retinal vascular endothelial cells (ACBRI-181) were also evaluated. CKS1B short hairpin RNA (shRNA) sequences (shRNA CKS1B-1, shRNA CKS1B-2 and shRNA CKS1B-3) and negative control shRNA sequences were constructed and transfected into cells at the third generation to evaluate the role of shCKS1B and the MEK/ERK signaling pathway in RB. Furthermore, the effect of shCKS1B on cell proliferation, migration, invasion, apoptosis and angiogenesis was investigated. CKS1B was determined to be highly expressed in RB tissue, compared with adjacent retina tissue. SO-RB50 and HXO-RB44 cells treated with shRNA CKS1B-1 and shRNA CKS1B-2 were selected for the present experiments. Activation of the MEK/ERK signaling pathway increases the expression of MEK, ERK, B-cell lymphoma 2, proliferating cell nuclear antigen, cyclin D1, vascular endothelia growth factor and basic fibroblast growth factor, enhances cell proliferation, migration, invasion and lumen formation, and decreases apoptosis. Following silencing CKS1B, the aforementioned conditions were reversed. The key observations of the present study demonstrated that shCKS1B can inhibit the proliferation, invasion and angiogenesis of RB cells by suppressing the MEK/ERK signaling pathway. Thus, CKS1B represents a potential research target in the development of therapeutics for RB.

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Cholera toxin subunit B (CTB) and Fluorogold(FG) are two widely utilized retrograde tracers to assess the number and function of retinal ganglion cells (RGCs). However, the relative advantages and disadvantages of these tracers remain unclear, which may lead to their inappropriate application. In this study, we compared these tracers by separately injecting the tracer into the superior Colliculi (SC) in rats, one or 2 weeks later, the rats were sacrificed, and their retinas, brains, and optic nerves were collected. From the first to second week, FG displayed a greater number of labeled RGCs and a larger diffusion area in the SC than CTB; The number of CTB labeled RGCs and the diffusion area of CTB in the SC increased significantly, but there was no distinction between FG; Furthermore, CTB exhibited more labeled RGC neurites and longer neurites than FG, but no difference was evident between the same trace; The optic nerves labeled using CTB were much clearer than those labeled using FG. In conclusion, both CTB and FG can be used for the retrograde labeling of RGCs in rats at 1 or 2 weeks. FG achieves retrograde labeling of a greater number of RGCs than CTB, whereas CTB better delineates the morphology of RGCs. Furthermore, CTB seems more suitable for retrograde labeling of some small, non-image forming nuclei in the brain to which certain RGC subtypes project their axons.

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