Recombinant Human Clusterin Seals Damage to the Ocular Surface Barrier in a Mouse Model of Ophthalmic Preservative-Induced Epitheliopathy

Chintala, Shravan K.; Pan, Jinhong; Satapathy, Sandeep; Condruti, Rebecca; Hao, Zixuan; Liu, Peiwen; O’Conner, Christian F.; Barr, Joseph T.; Wilson, Mark R.; Jeong, Shinwu; Fini, M. Elizabeth

doi:10.3390/ijms24020981

Cited by 1 publication

(1 citation statement)

References 79 publications

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“…Furthermore, a recent study established a correlation between low CLU concentration in tears and positive Schirmer strips test results (Schirmer strips being commonly used in research to assess tear production and therefore DED) [233]. Based on mice models, CLU was also hypothesized to bind selectively to damaged corneal surface and act as a wound healing mediator by sealing deficits in the epithelial barrier, preventing proteolysis due to MMP activation and reducing damage related to apoptosis and protein denaturation [234,268]. CLU was also found to promote corneal epithelial cell proliferation indirectly via upregulation of HGF (hepatocyte growth factor) [229].…”

Section: Dmmentioning

confidence: 99%

The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing

Gross,

Guérin,

Socol

et al. 2023

IJMS

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Clusterin (CLU) is a glycoprotein originally discovered in 1983 in ram testis fluid. Rapidly observed in other tissues, it was initially given various names based on its function in different tissues. In 1992, it was finally named CLU by consensus. Nearly omnipresent in human tissues, CLU is strongly expressed at fluid–tissue interfaces, including in the eye and in particular the cornea. Recent research has identified different forms of CLU, with the most prominent being a 75–80 kDa heterodimeric protein that is secreted. Another truncated version of CLU (55 kDa) is localized to the nucleus and exerts pro-apoptotic activities. CLU has been reported to be involved in various physiological processes such as sperm maturation, lipid transportation, complement inhibition and chaperone activity. CLU was also reported to exert important functions in tissue remodeling, cell–cell adhesion, cell–substratum interaction, cytoprotection, apoptotic cell death, cell proliferation and migration. Hence, this protein is sparking interest in tissue wound healing. Moreover, CLU gene expression is finely regulated by cytokines, growth factors and stress-inducing agents, leading to abnormally elevated levels of CLU in many states of cellular disturbance, including cancer and neurodegenerative conditions. In the eye, CLU expression has been reported as being severely increased in several pathologies, such as age-related macular degeneration and Fuch’s corneal dystrophy, while it is depleted in others, such as pathologic keratinization. Nevertheless, the precise role of CLU in the development of ocular pathologies has yet to be deciphered. The question of whether CLU expression is influenced by these disorders or contributes to them remains open. In this article, we review the actual knowledge about CLU at both the protein and gene expression level in wound healing, and explore the possibility that CLU is a key factor in cancer and eye diseases. Understanding the expression and regulation of CLU could lead to the development of novel therapeutics for promoting wound healing.

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