Characterization of full-length recombinant human Proteoglycan 4 as an ocular surface boundary lubricant

Samsom, Michael; Morrison, Sheila; Masala, Nemanja; Sullivan, Benjamin D.; Sullivan, David A.; Sheardown, Heather; Schmidt, Tannin A.

doi:10.1016/j.exer.2014.06.015

Cited by 89 publications

(106 citation statements)

References 21 publications

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“…Collectively, the methods and results of this study provide the framework for future development and assessment of novel low friction contact lens materials and lubricants. PRG4, specifically the recently available recombinant human PRG4 [58], may have clinical utility in reducing friction of contact lenses, either as a topically applied lubricant or being covalently link to lens surface, and therefore improving in vivo comfort. …”

Section: Resultsmentioning

confidence: 99%

In vitro friction testing of contact lenses and human ocular tissues: Effect of proteoglycan 4 (PRG4)

Samsom

Chan

Iwabuchi

et al. 2015

Tribology International

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Section: Resultsmentioning

confidence: 99%

In vitro friction testing of contact lenses and human ocular tissues: Effect of proteoglycan 4 (PRG4)

Samsom

Chan

Iwabuchi

et al. 2015

Tribology International

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“…On the contrary, exogenous application of lubricin, significantly reduces the friction between the cornea and conjunctiva. In a recent clinical trial, the researchers stated the efficacy and safety of recombinant human lubricin that was compared to a 0.18% hyaluronic acid (HA) eye drop in 39 subjects with moderate DE [89,90].…”

Section: New Topical Natural Substancementioning

confidence: 99%

“…This superficial zone protein containing a 1404-aminoacid core, is produced by ocular surface epithelia, and acts to protect the cornea and conjunctiva against shear forces generated during an eyelid blink [88,89].…”

Section: New Topical Natural Substancementioning

confidence: 99%

See 1 more Smart Citation

Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders

Nebbioso¹,

Regno²,

Gharbiya³

et al. 2017

Preprint

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The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome, because the tear film represents the interface between the eye and the environment. Despite having a multifactorial origin, the main risk factors for the emergence of the ocular disease are female gender and advanced age. Peer-reviewed version available at Int. J. Mol. Sci. 2017, 18, 1764 doi:10.3390/ijms18081764 2 Likewise, morphological changes in several glands and in chemical composition of their secretions such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors to maintain a condition of good health of the ocular anterior segment. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic infiammation that reflex on the ocular surface. However, it is one of the most commonly encountered disease in clinical practice and many other causes related to daily life and to lengthen the average life will contribute to the beginning. This review will consider how and what disorders of the ocular surface are responsible for a widespread pathology so. In the end, the most appropriate and new therapies will be briefly exposed according to the specific pathology.

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“…A third example is PRG4, a mucinlike secreted glycoprotein localized to the ocular surface, where it functions as a boundary lubricant [209]. PRG4, also called lubricin, may have clinical utility as a topical treatment for dry eye, or as a contact lens biomaterial coating to promote more comfortable wear [210].…”

Section: Clu As a Possible Biotherapeutic For Dry Eyementioning

confidence: 99%

Clusterin in the eye: An old dog with new tricks at the ocular surface

Fini

Bauskar

Jeong

et al. 2016

Experimental Eye Research

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, M. R. (2016). Clusterin in the eye: an old dog with new tricks at the ocular surface. Experimental Eye Research, Clusterin in the eye: an old dog with new tricks at the ocular surface AbstractThe multifunctional protein clusterin (CLU) was first described in 1983 as a secreted glycoprotein present in ram rete testis fluid that enhanced aggregation ('clustering') of a variety of cells in vitro. It was also independently discovered in a number of other systems. By the early 1990s, CLU was known under many names and its expression had been demonstrated throughout the body, including in the eye. Its homeostatic activities in proteostasis, cytoprotection, and anti-inflammation have been well documented, however its roles in health and disease are still not well understood. CLU is prominent at fluid-tissue interfaces, and in 1996 it was demonstrated to be the most highly expressed transcript in the human cornea, the protein product being localized to the apical layers of the mucosal epithelia of the cornea and conjunctiva. CLU protein is also present in human tears. Using a preclinical mouse model for desiccating stress that mimics human dry eye disease, the authors recently demonstrated that CLU prevents and ameliorates ocular surface barrier disruption by a remarkable sealing mechanism dependent on attainment of a critical all-or-none concentration in the tears. When the CLU level drops below the critical all-or-none threshold, the barrier becomes vulnerable to desiccating stress. CLU binds selectively to the ocular surface subjected to desiccating stress in vivo, and in vitro to LGALS3 (galectin-3), a key barrier component. Positioned in this way, CLU not only physically seals the ocular surface barrier, but it also protects the barrier cells and prevents further damage to barrier structure. CLU depletion from the ocular surface epithelia is seen in a variety of inflammatory conditions in humans and mice that lead to squamous metaplasia and a keratinized epithelium. This suggests that CLU might have a specific role in maintaining mucosal epithelial differentiation, an idea that can now be tested using the mouse model for desiccating stress. Most excitingly, the new findings suggest that CLU could serve as a novel biotherapeutic for dry eye disease. Competing Interests: US patent 9,241,974 B2 entitled "Clusterin pharmaceuticals and treatment methods using the same" (inventors: MEF and SJ), assigned to the University of Southern California, is connected with this work. MEF holds a management position with Proteris Biotech, Inc., Pasadena, CA, which is developing Protearin for dry eye based on clusterin. MRW declares that he has no competing interests. Page 3 of 65 AbstractThe multifunctional protein clusterin (CLU) was first described in 1983 as a secreted glycoprotein present in ram rete testis fluid that enhanced aggregation ('clustering') of a variety of cells in vitro. It was also independently discovered in a number of other systems. By the early 1990s, CLU was known under many names and its expression had bee...

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Characterization of full-length recombinant human Proteoglycan 4 as an ocular surface boundary lubricant

Cited by 89 publications

References 21 publications

In vitro friction testing of contact lenses and human ocular tissues: Effect of proteoglycan 4 (PRG4)

In vitro friction testing of contact lenses and human ocular tissues: Effect of proteoglycan 4 (PRG4)

Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders

Clusterin in the eye: An old dog with new tricks at the ocular surface

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