Proteases and Their Potential Role as Biomarkers and Drug Targets in Dry Eye Disease and Ocular Surface Dysfunction

Ramos-Llorca, Alba; Scarpellini, Camilla; Augustyns, Koen

doi:10.3390/ijms23179795

Cited by 6 publications

(4 citation statements)

References 128 publications

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“…Several previous studies have noted that proteolytic cleavage is a major potential drawback in the application of antimicrobial peptides [ 56 , 57 , 58 ]. Tears contain a variety of proteases, including tryptase from mast cells and NSP4 from neutrophils that both have trypsin-like activity [ 30 , 34 ]. Trypsin cleaves amino acids from proteins at lysine and arginine residues when these are not linked to a C-terminal proline.…”

Section: Discussionmentioning

confidence: 99%

“…MMP-8, MMP-9 and cathepsin-S have been found at the highest concentrations in tears [ 29 ]. Tryptase from mast cells has trypsin-like activity (i.e., cleaves peptides at arginine (R) or lysine (K) amino acids) and has been found in tears [ 30 ]. Interestingly, mast cells, which reside in the conjunctiva, can be stimulated to release their contents by antimicrobial peptides [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Deposition and Protease Digestion on the Ex Vivo Activity of Antimicrobial Peptide-Coated Contact Lenses

et al. 2023

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A clinical study of antimicrobial contact lenses containing the cationic peptide Mel4 was conducted. The few adverse events that occurred with this lens occurred on or after 13 nights of wear. The current study examined whether the Mel4 contact lenses lost activity during wear and the mechanism of this loss. Participants wore contact lenses for up to 13 nights. Lenses were tested for their ability to reduce the adhesion of Pseudomonas aeruginosa and Staphylococcus aureus. The amount of protein and lipid extracted from lenses was measured. The ability of trypsin to affect the antimicrobial activity of Mel4-coated contact lenses was measured. Mel4-coated contact lenses lost their antimicrobial activity at six nights of wear for both bacteria. The amount of lipids (13 ± 11 vs. 21 ± 14 μg/lens at 13 nights wear) and proteins (8 ± 4 vs. 10 ± 3 mg/lens at 13 nights of wear) extracted from lenses was not different between Mel4-coated and uncoated lenses, and was not different after three nights when antimicrobial activity was maintained and thirteen nights when they had lost activity (lipid: 25 ± 17 vs. 13 ± 11, p = 0.2; protein: 8 ± 1 vs. 8 ± 4 mg/lens, p = 0.4). Trypsin digestion eliminated the antimicrobial activity of Mel4-coated lenses. In summary, Mel4-coated contact lenses lost antibacterial activity at six nights of wear, and the most likely reason was proteolytic digestion of the peptide. Future studies will design and test proteolytically stable peptide mimics as coatings for contact lenses.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Deposition and Protease Digestion on the Ex Vivo Activity of Antimicrobial Peptide-Coated Contact Lenses

et al. 2023

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“…Tryptase secreted by mast cells also plays an important role in the pathology of dry eye, promoting the expression and activation of pro-inflammatory cytokines, affecting the degradation of extracellular matrix components and the loss of epithelial barrier function. 64 In addition, tryptase activates corneal PAR2 receptors, which in turn activate MAPK and NF-κB signalling pathways to continue to enhance the local inflammatory response. Furthermore, PAR2 receptors are also associated with neuropathic pain, which may be clinically relevant to the ocular pain felt by some patients with dry eyes.…”

Section: Research In Ophthalmic Diseasementioning

confidence: 99%

Tryptase and Exogenous Trypsin: Mechanisms and Ophthalmic Applications

Li¹,

Lu²,

Li³

et al. 2023

JIR

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Ocular injuries caused by inflammation, surgery or accidents are subject to a physiological healing process that ultimately restores the structure and function of the damaged tissue. Tryptase and trypsin are essential component of this process and they play a role in promoting and reducing the inflammatory response of tissues, respectively. Following injury, tryptase is endogenously produced by mast cells and can exacerbate the inflammatory response both by stimulating neutrophil secretion, and through its agonist action on proteinase-activated receptor 2 (PAR2). In contrast, exogenously introduced trypsin promotes wound healing by attenuating inflammatory responses, reducing oedema and protecting against infection. Thus, trypsin may help resolve ocular inflammatory symptoms and promote faster recovery from acute tissue injury associated with ophthalmic diseases. This article describes the roles of tryptase and exogenous trypsin in affected tissues after onset of ocular injury, and the clinical applications of trypsin injection.

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“…Протеазы играют ключевую роль в воспалении и считаются терапевтическими мишенями и биомаркерами при ССГ [54]. В ряде исследований было показано, что MMP-9 влияет на воспалительные пути и иммунные реакции при ССГ, а также коррелирует с тяжестью течения ССГ [54,55].…”

Section: диагностика синдрома сухого глазаunclassified

Dry Eye Syndrome in Refractive Patients. Literature Review

Doga,

Borzenok,

Mushkova

et al. 2023

Oftalʹmologiâ

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Dry eye syndrome is a multifactorial disease of the ocular surface, which is based on the development of hyperosmolarity, inflammation and sensorineural disorders in the imbalance of the structural components of the tear film. The main complaints of refractive patients after keratorefractive surgery are a feeling of dryness in the eyes, a foreign body, redness, blurring of the image, which is due to the clinical manifestations of post-refractive dry eye syndrome. There are factors that contribute to the development of postrefractive dry eye syndrome, such as: neurotrophic epitheliopathy, postoperative inflammation, damage to goblet cells, toxic corneal epitheliopathy caused by preservatives contained in eye drops, leading to inadequate restoration of the tear film. In clinical practice, to assess the stability of the tear film, a method is used to determine the tear film rupture time using invasive and non-invasive methods. Invasive methods include: staining of the ocular surface with a solution of fluorescein during the Norn test. To date, laboratory diagnostics expands the understanding of the pathogenesis, etiology and mechanisms underlying the xerosis of the ocular surface at the molecular level, and also facilitates the diagnosis and prognosis of dry eye syndrome. Laboratory methods of the ocular surface include the study of biomarkers of lacrimal fluid, conducting impression cytology with an assessment of the condition of goblet cells. In this regard, it is necessary to have a deep understanding of the main etiopathogenetic links of dry eye syndrome, a wide range of diagnostics of the condition of the ocular surface before and after the surgical stage of patient management, which will determine the success of keratorefractive surgery and a stable course of the postoperative period.

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Proteases and Their Potential Role as Biomarkers and Drug Targets in Dry Eye Disease and Ocular Surface Dysfunction

Cited by 6 publications

References 128 publications

Effect of Deposition and Protease Digestion on the Ex Vivo Activity of Antimicrobial Peptide-Coated Contact Lenses

Effect of Deposition and Protease Digestion on the Ex Vivo Activity of Antimicrobial Peptide-Coated Contact Lenses

Tryptase and Exogenous Trypsin: Mechanisms and Ophthalmic Applications

Dry Eye Syndrome in Refractive Patients. Literature Review

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