Chao Xing

Bio: Chao Xing is an academic researcher from Fudan University. The author has contributed to research in topics: Pyroptosis & Inflammasome. The author has an hindex of 4, co-authored 5 publications receiving 63 citations.

Airborne particulate matter (PM 2.5 ) triggers ocular hypertension and glaucoma through pyroptosis.

Abstract: Particulate matter (PM) is strongly linked to human health and has detrimental effects on the eye. Studies have, however, focused on the ocular surface, with limited research on the impact of PM2.5 on intraocular pressure (IOP). To investigate the impact of PM2.5 on IOP and the associated mechanism, C57BL/6 mouse eyes were topically exposed to a PM2.5 suspension for 3 months, and human trabecular meshwork (HTM) cells were subjected to various PM2.5 concentrations in vitro. Cell viability, NLRP3/caspase-1, IL-1β, and GSDMD expression, reactive oxygen species (ROS) production and cell contractility were measured by western blot, ELISA, cell counting kit-8, ROS assay kit or a cell contractility assay. ROS scavenger N-acetyl-L-cysteine (NAC) and caspase-1 inhibitor VX-765 were used to intervene in PM2.5-induced damages. The results revealed that the IOP increased gradually after PM2.5 exposure, and upregulations of the NLRP3 inflammasome, caspase-1, IL-1β, and GSDMD protein levels were observed in outflow tissues. PM2.5 exposure decreased HTM cell viability and affected contraction. Furthermore, elevated ROS levels were observed as well as an activation of the NLRP3 inflammasome and downstream inflammatory factors caspase-1 and IL-1β. NAC improved HTM cell viability, inhibited the activation of the NLRP3 inflammasome axis, and HTM cell contraction by scavenging ROS. VX-765 showed similar protection against the PM2.5 induced adverse effects. This study provides novel evidence that PM2.5 has a direct toxic effect on intraocular tissues and may contribute to the initiation and development of ocular hypertension and glaucoma. This occurs as a result of increased oxidative stress and the subsequent induction of NLRP3 inflammasome mediated pyroptosis in trabecular meshwork cells.

eNOS Activity in CAV1 Knockout Mouse Eyes.

Abstract: PURPOSE To investigate endothelial nitric oxide synthase (eNOS) activity and the response of conventional outflow facility to nitric oxide donors and a nitric oxide synthase (NOS) inhibitor in caveolin-1 (CAV1) knockout (KO) mice. METHODS Intraocular pressure (IOP) was measured in both CAV1 KO and wild-type (WT) mice by rebound tonometry. The expressions of caveolin-2 (CAV2), eNOS, eNOS-phospho Ser1177, eNOS-phospho Thr495, Akt, Akt-phospho Ser473, and nitrotyrosin were measured by Western blot analysis. Nitric oxide donor sodium nitroprusside (SNP), S-nitroso-N-acetyl-D,L-penicillamine (SNAP), or the NOS inhibitor L-NG-Nitroarginine Methyl Ester (L-NAME) were administered topically. The outflow facility was measured by perfusing enucleated mouse eyes at multiple pressure steps. RESULTS CAV1 KO mice have elevated IOP and reduced conventional outflow facility when compared with WT mice. CAV2 expression was absent in CAV1 KO mice, but we observed increased expressions of eNOS, eNOS-phospho Ser1177, Akt, Akt-phospho Ser473, and nitrotyrosin and reduced expression of eNOS-phospho Thr495. Topical application of SNP significantly reduced IOP in WT and KO mice by 1.6 fold (n = 6, P 0.05). In comparison, the NOS inhibitor L-NAME significantly increased IOP by 50% in KO mice (n = 6, P < 0.05). SNP and SNAP significantly increased, whereas L-NAME significantly reduced pressure-dependent drainage in KO animals. CONCLUSIONS Although CAV1 KO mice had elevated IOP and decreased outflow facility, CAV1 deficiency (and possibly the loss of CAV2) resulted in increased eNOS activity. The pressure elevation may be a result of increased tyrosine nitration of protein kinase K and impairment of its activity in KO mice.

Airborne particulate matter (PM2.5) triggers ocular hypertension through pyroptosis

Abstract: Liping Li Fudan University Eye Ear Nose and Throat Hospital https://orcid.org/0000-0002-0257-0037 Chao Xing Fudan University Eye Ear Nose and Throat Hospital Liangliang Niu Fudan University Eye Ear Nose and Throat Hospital Bin Luo Lanzhou University Ji Zhou Shanghai Meteorological Bureau Maomao Song Fudan University Eye Ear Nose and Throat Hospital Jingping Niu Lanzhou University Ye Ruan Lanzhou University Xinghuai Sun Fudan University Eye Ear Nose and Throat Hospital Yuan Lei (  lilian0167@hotmail.com ) Fudan University Eye Ear Nose and Throat Hospital

Caveolin-1 modulates intraocular pressure: implications for caveolae mechanoprotection in glaucoma

Abstract: Polymorphisms in the CAV1/2 genes that encode signature proteins of caveolae are associated with glaucoma, the second leading cause of blindness worldwide, and with its major risk factor, intraocular pressure (IOP). We hypothesized that caveolin-1 (Cav-1) participates in IOP maintenance via modulation of aqueous humor drainage from the eye. We localize caveolae proteins to human and murine conventional drainage tissues and show that caveolae respond to mechanical stimulation. We show that Cav-1-deficient (Cav-1-/-) mice display ocular hypertension explained by reduced pressure-dependent drainage of aqueous humor. Cav-1 deficiency results in loss of caveolae in the Schlemm's canal (SC) and trabecular meshwork. However, their absence did not appear to impact development nor adult form of the conventional outflow tissues according to rigorous quantitative ultrastructural analyses, but did affect cell and tissue behavior. Thus, when IOP is experimentally elevated, cells of the Cav-1-/- outflow tissues are more susceptible to plasma membrane rupture indicating that caveolae play a role in mechanoprotection. Additionally, aqueous drainage from Cav-1-/- eyes was more sensitive to nitric oxide (NO) synthase inhibition than controls, suggesting that excess NO partially compensates for outflow pathway dysfunction. These results provide a functional link between a glaucoma risk gene and glaucoma-relevant pathophysiology.

Local Delivery and Sustained-Release of Nitric Oxide Donor Loaded in Mesoporous Silica Particles for Efficient Treatment of Primary Open-Angle Glaucoma.

Abstract: Nitric oxide (NO) donors are ideal drug candidates for reducing intraocular pressure in the treatment of glaucoma. However, poor cornea penetration, short duration of efficacy, and narrow therapeutic index of most NO donors obstruct their clinical applications in glaucoma treatment. This study reports a novel NO donor delivery system based on mesoporous silica nanoparticles that can readily overcome the above difficulties and deliver the NO-donating drug sodium nitroprusside to the target tissues (trabecular meshwork and Schlemm's canal). Mesoporous silica nanoparticles loaded with sodium nitroprusside can produce more exogenous NO and sustain higher NO concentration in animal eye models, which significantly extend the duration of intraocular pressure reduction from 3 to 48 h with only 1/40 of the dose of sodium nitroprusside solution. These findings open up the possibility of mesoporous silica nanoparticles loading sodium nitroprusside for effective management of ocular hypertension.

Caveolin-1 and Caveolin-2 Can Be Antagonistic Partners in Inflammation and Beyond.

Abstract: Caveolins, encoded by the CAV gene family, are the main protein components of caveolae. In most tissues, caveolin-1 (Cav-1) and caveolin-2 (Cav-2) are co-expressed, and Cav-2 targeting to caveolae depends on the formation of heterooligomers with Cav-1. Notwithstanding, Cav-2 has unpredictable activities, opposing Cav-1 in the regulation of some cellular processes. While the major roles of Cav-1 as a modulator of cell signaling in inflammatory processes and in immune responses have been extensively discussed elsewhere, the aim of this review is to focus on data revealing the distinct activity of Cav-1 and Cav-2, which suggest that these proteins act antagonistically to fine-tune a variety of cellular processes relevant to inflammation.