Towards a dynamic customised therapy for ocular surface dysfunctions

Aragona, Pasquale; Rolando, Maurizio

doi:10.1136/bjophthalmol-2012-302568

Cited by 44 publications

(37 citation statements)

References 34 publications

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“…However, reliable assessment of DED severity can be problematic due to several issues, including poorly standardised evaluation methods, non-correlation between disease severity and clinical/biological disease markers, and individual variability in symptomatology and disease signs. The vicious circle of DED pathogenesis, which can exacerbate the condition and facilitate merging or development of mechanistically distinct DED subtypes can further hinder accurate evaluation 21 13 22 42…”

Section: Discussionmentioning

confidence: 99%

Diagnosing the severity of dry eye: a clear and practical algorithm

et al. 2014

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Dry eye disease (DED) is a distressing ocular condition. Due to its multifactorial nature, clinical and biological signs of DED can be inconsistent and sometimes discordant with symptomatology. Consequently, no gold-standard model for determining DED severity exists. This can impact treatment decisions and complicate evaluation of disease progression, particularly within the stringent context of clinical trials. The multinational ODISSEY European Consensus Group is comprised of ophthalmologists who contend with ocular surface disease issues on a daily basis. This group convened to establish a clear and practical algorithm for evaluation and diagnosis of severe DED. Using a consensus-based approach, they assessed 14 commonly used DED severity criteria. The panel agreed that following confirmed DED diagnosis, just two criteria, symptom-based assessment and corneal fluorescein staining were sufficient to diagnose the presence of severe DED in the majority of patients. In the event of discordance between signs and symptoms, further evaluation using additional determinant criteria was recommended. This report presents the ODISSEY European Consensus Group recommended algorithm for DED evaluation, which facilitates diagnosis of severe disease even in the event of discordance between signs and symptoms. It is intended that this algorithm will be useful in a clinical and developmental setting.

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Section: Discussionmentioning

confidence: 99%

Diagnosing the severity of dry eye: a clear and practical algorithm

et al. 2014

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“…6,7 If the inflammatory response is self-limiting, it can hasten restoration of corneal epithelial integrity and function by promoting wound healing through suppressing pathogenic infiltration. 8 Even though some of the sequelae subsequent to hypertonicity-induced ROS generation have been characterized, it is unknown whether transient receptor potential melastatin 2 (TRPM2) channels are a biosensor of hyperosmotic and oxidative stress and trigger activation of this signaling axis in human corneal epithelial cells (HCECs).…”

Section: Resultsmentioning

confidence: 99%

Hyperosmotic Stress–Induced TRPM2 Channel Activation Stimulates NLRP3 Inflammasome Activity in Primary Human Corneal Epithelial Cells

Zheng

Tan

Ren

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The purpose of this study was to determine whether either a hyperosmotic or oxidative stress induces NLRP3 inflammasome activation and increases in bioactive IL-1b secretion through transient receptor potential melastatin 2 (TRPM2) activation in primary human corneal epithelial cells (PHCECs). METHODS.Real-time PCR, Western blots, and immunofluorescent staining were used to evaluate TRPM2 and NLRP3, ASC, caspase-1, and IL-1b mRNA and protein expression levels, respectively. A CCK-8 assay evaluated cell viability. Hyperosmotic 500 mOsm and oxidative 0.5 mM H 2 O 2 stresses were imposed. TRPM2 expression was inhibited with a TRPM2 inhibitor, 20 lM N-(p-amylcinnamoyl) anthranilic acid (ACA), or TRPM2 siRNA knockdown.RESULTS. In the hypertonic medium, TRPM2, NLRP3, ASC, caspase-1, and IL-1b gene and protein expression levels rose after 4 hours (P 0.043), whereas ACA preincubation suppressed these rises (P 0.044). Similarly, H 2 O 2 upregulated TRPM2 protein expression by 80%, and induced both NLRP3 inflammasome activation and increased bioactive IL-1b secretion (P 0.036), whereas ACA pretreatment suppressed these effects (P 0.029). TRPM2 siRNA transfection reduced TRPM2 gene expression by 70% (P ¼ 0.018) in this hyperosmotic medium and inhibited the increases in NLRP3, caspase-1, and IL-1b gene (P 0.028) and protein expression (P 0.037).CONCLUSIONS. TRPM2 activation by either a hyperosmotic or oxidative stress contributes to mediating increases in NLRP3 inflammasome activity and bioactive IL-1b expression because inhibiting TRPM2 activation or its expression blunted both of these responses in PHCECs. This association points to the possibility that TRPM2 is a viable target to suppress hyperosmotic-induced corneal epithelial inflammation.

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“…164 The need for patientoriented therapy has also been claimed for postmenopausal HT 165 and ocular surface diseases. 166,167 Hormonal supplementation stands upon the basic consideration that a lowering in bioavailable hormone(s) exists in a given system. Clinical characteristics and potential biomarkers should be identified to guide the HT strategy in those DE suffering women who would be most likely to benefit from treatment.…”

Section: Hormone Therapymentioning

confidence: 99%

Sex-Steroid Imbalance in Females and Dry Eye

Versura

Giannaccare

Campos

2014

Current Eye Research

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Dry eye (DE) is a multifactorial disorder of the ocular surface unit that results in eye discomfort, visual disturbance and ocular surface damage. It is one of the most common complaints in daily ophthalmic practice. The risk of DE increases with age in both sexes, while its incidence is higher among females. In addition, the condition of menopause in aging women may also contribute to DE onset or worsening as a consequence of an overall hormonal imbalance. Sex hormones play a key role in ocular surface physiology and they impact differently on ocular surface tissues. Reduced estrogen levels were historically thought to be responsible in age-related DE onset but more recent investigations have reconsidered the role of androgens that are present and exert a protective function on the ocular surface. Hormone levels themselves, withdrawal changes in hormone levels, and the changes in hormone-receptor responsiveness are all important factors but it remains to be fully elucidated how estrogen or androgen insufficiency act alone or together in a combined imbalance or interplay to raise the risk of disease. The purpose of this review is to briefly outline current scientific evidence on the influence of androgens and estrogens, on the Lachrymal and Meibomian glands and on ocular surface epithelia including conjunctival goblet cells during reproductive and menopausal periods. The role of sex steroids is also discussed in relation to the pathogenesis of different forms of DE and Sjogren's syndrome (SS). The impact of systemic hormone therapy (HT) in DE post-menopausal women still appears as a controversial issue, despite the many clinical studies. Finally, the outcomes of topical applications of steroid-based products are summarized, underlying the need for potential (tear) biomarker(s) in the rationale of DE-targeted therapy.

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Towards a dynamic customised therapy for ocular surface dysfunctions

Cited by 44 publications

References 34 publications

Diagnosing the severity of dry eye: a clear and practical algorithm

Diagnosing the severity of dry eye: a clear and practical algorithm

Hyperosmotic Stress–Induced TRPM2 Channel Activation Stimulates NLRP3 Inflammasome Activity in Primary Human Corneal Epithelial Cells

Sex-Steroid Imbalance in Females and Dry Eye

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