scholarly journals A synthetic metalloporphyrin SOD mimetic protects corneal epithelial cells from oxidative stress‐induced damage in vitro and in vivo

2018 ◽  
Vol 96 (S261) ◽  
pp. 124-124
Alcohol ◽  
2021 ◽  
Vol 96 ◽  
pp. 101
Author(s):  
Anita K. Ghosh ◽  
Robertas Cesna ◽  
Agne Žiniauskaitė ◽  
Donatas Neverauskas ◽  
Jonathan M. Eby ◽  
...  

Author(s):  
Anita Kirti Ghosh ◽  
Rubina Thapa ◽  
Harsh Nilesh Hariani ◽  
Michael Volyanyuk ◽  
Karoline Anne Orloff ◽  
...  

Elevated levels of oxidative stress in the corneal epithelium contribute to the progression of dry eye disease pathology. Previous studies have shown that antioxidant therapeutic intervention is a promising avenue to reduce disease burden and slow disease progression. In this study, we evaluated the pharmacological efficacy of Xanthohumol in preclinical models for dry eye disease. Xanthohumol is a naturally occurring prenylated chalconoid that promotes the transcription of phase II antioxidant enzymes. Xanthohumol exerted a dose-response in preventing tert-butylhydroxide-induced loss of cell viability in human corneal epithelial (HCE-T) cells and resulted in a significant increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of the endogenous antioxidant system. Xanthohumol-encapsulating poly(lactic-co-glycolic acid) nanoparticles (PLGA NP) were cytoprotective against oxidative stress in vitro, and significantly reduced corneal fluorescein staining in the mouse desiccating stress/ scopolamine model for dry eye disease in vivo by reducing oxidative stress-associated DNA damage in corneal epithelial cells. PLGA NP represent a safe and efficacious drug delivery vehicle for hydrophobic small molecules to the ocular surface. Optimization of NP-based antioxidant formulations with the goal to minimize instillation frequency may represent future therapeutic options for dry eye disease and related ocular surface disease.


2017 ◽  
Vol 43 (2) ◽  
pp. 801-811 ◽  
Author(s):  
Hao Cui ◽  
Ying Liu ◽  
Yifei Huang

Background: Epithelial cells play important roles as a critical barrier in protecting the cornea from microbial pathogens infection. Methods: In this study, we were aiming to investigate the role of E3 ubiquitin ligase tripartite motif protein 32 (TRIM32) in corneal epithelial cells in response to Herpes Simplex Virus type 1 (HSV-1) infection and to elucidate the underlying mechanisms. Results: We found the expression of TRIM32 was increased after infected with HSV-1 both in murine corneas and cultured human epithelial (HCE) cells. Furthermore, knockdown of the expression of TRIM32 significantly aggravated HSV-1 induced herpetic stromal keratitis (HSK) in mice and promoted the replication of HSV-1 in cultured HCE cells. We also observed that silencing of TRIM32 resulted in the decreased expression of IFN-β and suppressed activation of interferon regulatory factor 3 (IRF3) both in vivo and in vitro. Finally, we found TRIM32 positively regulate IFN-β production in corneal epithelial cells through promoting K63-linked polyubiquitination of stimulator of interferon genes (STING). Conclusion: In conclusion, our data suggested that TRIM32 as a crucial positive regulator of HSV-1 induced IFN-β production in corneal epithelial cells, and it played a predominant role in clearing HSV-1 from the cornea.


2003 ◽  
Vol 71 (9) ◽  
pp. 5389-5393 ◽  
Author(s):  
Irandokht Zolfaghar ◽  
David J. Evans ◽  
Suzanne M. J. Fleiszig

ABSTRACT Twitching motility is a form of surface-associated bacterial movement mediated by type IV pili of Pseudomonas aeruginosa. Others have shown that pilT and pilU mutants, which are piliated but defective in twitching motility, display reduced cytotoxic capacity towards epithelial cells in vitro. Although these mutants efficiently infected lungs in vivo, they were defective in dissemination to the liver. In this study the role of twitching motility in P. aeruginosa epithelial cell invasion and corneal disease pathogenesis was explored. pilU and pilT mutants of P. aeruginosa strain PAK were compared to a nonpiliated pilA mutant and to wild-type bacteria in their ability to associate with and to invade corneal epithelial cells in vitro and to cause disease in a murine model of corneal infection. As expected, the pilA mutant demonstrated reduced association and invasion of corneal epithelial cells (P < 0.05 in both cases). The pilT mutant, but not the pilU mutant, was less invasive than wild-type PAK was (P < 0.05 versus P = 0.43), while both pilU and pilT mutants exhibited association levels similar to those of the wild type (P = 0.31 and 0.52, respectively). In vivo, all mutants were markedly attenuated in virulence and showed reduced ability to colonize the cornea at 4 and 48 h (all P values < 0.02). Thus, twitching motility contributed to the role of pili in corneal disease but was not involved in the role of pili in adherence to or invasion of corneal epithelial cells.


Cornea ◽  
2007 ◽  
Vol 26 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Marco Porcu ◽  
Francesco Guarna ◽  
Laura Formentini ◽  
Giuseppe Faraco ◽  
Silvia Fossati ◽  
...  

Cornea ◽  
2003 ◽  
Vol 22 (5) ◽  
pp. 468-472 ◽  
Author(s):  
Anna Claudia Scuderi ◽  
Grazia Maria Paladino ◽  
Clara Marino ◽  
Francesco Trombetta

1998 ◽  
Vol 17 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Shizuya Saika ◽  
Yoshiji Kawashima ◽  
Yuka Okada ◽  
Sai-Ichi Tanaka ◽  
Osamu Yamanaka ◽  
...  

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