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Pyroptosis, an inflammasome-mediated mode of death, plays an important role in glaucoma. It has been shown that regulating the mTOR pathway can inhibit pyroptosis. Unfortunately, whether rapamycin (RAPA), a specific inhibitor of the mTOR pathway, can inhibit optic nerve crush (ONC)-induced pyroptosis to protect retinal ganglion cells (RGCs) has not been investigated. Our research aimed to confirm the effect of intravitreal injection of RAPA on RGCs. Furthermore, we used the ONC model to explore the underlying mechanisms. First, we observed that intravitreal injection of RAPA alleviated RGC damage induced by various types of injury. We then used the ONC model to further explore the potential mechanism of RAPA. Mechanistically, RAPA not only reduced the activation of glial cells in the retina but also inhibited retinal pyroptosis-induced expression of inflammatory factors such as nucleotide-binding oligomeric domain-like receptor 3 (NLRP3), apoptosis-associated speckle-like protein containing a CARD (ASC), N-terminal of gasdermin-D (GSDMD-N), IL-18 and IL-1β. Moreover, RAPA exerted protective effects on RGC axons, possibly by inhibiting glial activation and regulating the mTOR/ROCK pathway. Therefore, this study demonstrates a novel mechanism by which RAPA protects against glaucoma and provides further evidence for its application in preclinical studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Glaucoma is an ophthalmic disease that is characterized by elevated intraocular pressure (IOP). Eye drops are the preferred choice to reduce IOP for the treatment of glaucoma. However, the bioavailability of eye drops is low (<5%). Their long-term frequent administration cannot ensure patient compliance, which is the main reason for treatment failure. Inspired by lollipop, herein, a multilayered sodium alginate-chitosan (SA-CS) hydrogel ball (HB) decorated by zinc oxide-modified biochar (ZnO-BC) is developed as a new drug delivery system. The multilayer structure encapsulate timolol maleate (TM) and levofloxacin inside the different layers to realize the sustained release of drugs, which can control ocular hypertension and prevent infection effectively. The results show that the release of TM can be sustained in vitro for longer than 2 weeks. Moreover, IOP is also effectively reduced in vivo. Meanwhile, the photothermal conversion activity of ZnO-BC can regulate drug release on demand after stimulation by near-infrared irradiation. More importantly, the designed HB also shows good biocompatibility and antibacterial properties in vitro and in vivo. In summary, ZnO-BC-SA-CS HB can effectively reduce IOP and is expected to replace the classical tedious eye drop strategy, having potential utilization value in the treatment of glaucoma., (© 2021 Wiley-VCH GmbH.)

Glaucoma is a progressive optic neuropathy that has become the most common cause of irreversible blindness worldwide. Studies have shown that the protein mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a central role in regulating numerous functions, such as growth, proliferation, cytoskeletal organization, metabolism, and autophagy. Clinical trials have shown that Rho-associated protein kinase (ROCK) inhibitors reduced intraocular pressure (IOP) in patients with glaucoma and ocular hypertension (OHT). In this study, we explored whether rapamycin (RAPA) eye drops can reduce IOP and protect retinal ganglion cells (RGCs). Our results indicated that in rats treated with RAPA, the drug was detected in the aqueous humor (AH), and the IOP was reduced. This may be related to the inhibition of RhoA protein activation by RAPA and regulation of the actin cytoskeleton in trabecular meshwork (TM) cells. In addition, the retinal thickness and the survival rate of RGCs were significantly reduced in the OHT group compared with the control group. These changes in the OHT group were significantly improved after treatment with RAPA. This may be because RAPA inhibited the activation of glial cells and the release of proinflammatory factors, thereby attenuating further damage to the retina and RGCs. Taken together, the results of this study demonstrated that RAPA not only reduced IOP but also protected RGCs, suggesting that RAPA is likely to be an effective strategy for the treatment of glaucoma., (Copyright © 2020 Elsevier B.V. All rights reserved.)