Thymosin β4 inhibits benzalkonium chloride-mediated apoptosis in corneal and conjunctival epithelial cells in vitro

In Vitro Toxicity of Topical Ocular Prostaglandin Analogs and Preservatives on Corneal Epithelial Cells

“…Similar effects for BAK have been noted in numerous in vitro studies on human corneal and conjunctival epithelium and stroma. 15,[21][22][23][24] Alternative preservative systems such as the oxidizing preservative sofZia have been developed to potentially diminish the deleterious effects on epithelial cells after chronic exposures while still protecting multidose bottles from pathogen contamination. Oxidizing preservatives cause oxidative damage in bacteria and subsequent death due to the lack of oxidases and catalases in these organisms.…”

“…3,7,[9][10][11][12][13][14] BAK is the most common preservative used in topical ophthalmic medications and is believed to be a major cause of toxicity noted with PGA formulations. [15][16][17][18][19][20][21][22][23][24] BAK is a quaternary ammonium compound that acts as a detergent, disrupting bacterial cell membranes and ultimately leading to bacterial cell death. Similar effects for BAK have been noted in numerous in vitro studies on human corneal and conjunctival epithelium and stroma.…”

Thymosin beta-4 upregulates anti-oxidative enzymes and protects human cornea epithelial cells against oxidative damage

“…It has been postulated that exogenous Tβ 4 can be used ophthalmologically, as preclinical studies indicated that it promotes corneal wound healing and modulates inflammatory mediators in vivo,26 inhibits corneal epithelial cell apoptosis after ethanol exposure8 and inhibits benzalkonium chloride-mediated apoptosis in corneal and conjunctival epithelial cells 10. By demonstrating, for the first time, that exogenous Tβ 4 protects human corneal epithelial cells against intrinsic pathway-mediated apoptosis by reducing intracellular oxidative stress through enhancing the expression of several anti-oxidative enzymes, our results not only offered more mechanistic explanation about the protective mechanism of Tβ 4 but also supported further investigation towards the clinical use of this small molecule in treating and preventing oxidative damage of cornea.…”

“…Thymosin β-4 (Tβ 4 ), originally found as a G-actin sequestering protein, has been demonstrated to possess anti-apoptosis function, and its anti-apoptotic effects against ethanol,8 Fas ligand, and hydrogen peroxide (H 2 O 2 )9 have been shown in corneal epithelial cells and conjunctival cells 10. It is now appreciated that apoptosis triggered by H 2 O 2 is mainly mediated by the intrinsic signalling pathway, which is associated with increased intracellular oxidative stress 11 12.…”

Peptide therapies for ocular surface disturbances based on fibronectin–integrin interactions

“…Limbal stem cells serve as a reservoir for corneal epithelial cells, so that depletion or loss of function of these stem cells can result in a lack or deficiency of healthy (terminally differentiated) corneal epithelial cells and in the consequent development of persistent epithelial defects (Mort et al, 2012;Notara et al, 2010;OseiBempong et al, 2013;Secker and Daniels, 2008;Yoon et al, 2014) Thymosin b4 is a small protein of 43 amino acids (Low et al, 1981) that stimulates hair growth and corneal epithelial wound healing through promotion of stem cell migration, inhibition of corneal epithelial cell apoptosis, and an anti-inflammatory action (Philp et al, 2007;Sosne et al, 2001Sosne et al, , 2002Sosne et al, , 2004Sosne et al, , 2006Sosne et al, , 2007a. Clinically, thymosin b4 has been found to be effective for the treatment of neurotrophic keratopathy and dry eye syndrome (Dunn et al, 2010;Sosne et al, 2012).…”