Progressive retinal ganglion cells (RGCs) death that triggered by retinal ischemia reperfusion (IR), leads to irreversible visual impairment and blindness, but our knowledge of post-IR neuronal death and related mechanisms is limited. In this study, we first demonstrated that apart from necroptosis, which occurs before apoptosis, ferroptosis, which is characterized by iron deposition and lipid peroxidation, is involved in the whole course of retinal IR in mice. Correspondingly, all three types of RGCs death were found in retina samples from human glaucoma donors. Further, inhibitors of apoptosis, necroptosis, and ferroptosis (z-VAD-FMK, Necrostatin-1, and Ferrostatin-1, respectively) all exhibited marked RGC protection against IR both in mice and primary cultured RGCs, with Ferrostatin-1 conferring the best therapeutic effect, suggesting ferroptosis plays a more prominent role in the process of RGC death. We also found that activated microglia, Müller cells, immune responses, and intracellular reactive oxygen species accumulation following IR were significantly mitigated after each inhibitor treatment, albeit to varying degrees. Moreover, Ferrostatin-1 in combination with z-VAD-FMK and Necrostatin-1 prevented IR-induced RGC death better than any inhibitor alone. These findings stand to advance our knowledge of the post-IR RGC death cascade and guide future therapy for RGC protection.
Introduction:To compare 1-year outcomes of CO 2 laser-assisted sclerectomy surgery (CLASS) alone or combined with phacoemulsification (CLASS ? Phaco) in eyes with primary openangle glaucoma (POAG). Methods: This was a prospective, comparative, case series study. A total of 46 eyes with POAG underwent CLASS or CLASS ? Phaco were followed up for 1 year. The primary outcomes included changes in intraocular pressure (IOP), medication and best corrected visual acuity (BCVA). The secondary outcomes were success rate, functional bleb, postoperative laser intervention and complications. Results: CLASS alone resulted in a greater IOP reduction compared with CLASS ? Phaco. BCVA improved remarkably in CLASS ? Phaco group, but there was no difference in BCVA before and after CLASS. The number of antiglaucoma medications significantly decreased at 12 months postoperatively in both groups. Functional blebs were more commonly seen in the CLASS than combination group. The overall success rate was higher in the CLASS than CLASS ? Phaco group at 1 year after surgery. The incidence of peripheral anterior synechiae (PAS) in CLASS ? Phaco group was significantly lower than that of CLASS alone. Conclusion: CLASS alone achieved a greater IOP reduction, more common functional bleb formation and a higher success rate compared to CLASS combined with Phaco, while combination surgery yielded a better BCVA improvement and a lower PAS incidence than CLASS alone. Both surgical strategies have favorable safety and efficacy among POAG patients. Combined surgery could be a viable option for patients with co-existing POAG and cataract.
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