Hot Topics in Dry Eye Disease

Chiaradia, Pablo; Bardeci, Luis Alberto Zeman; Dankert, Sebastian; Mendaro, Marcos; Grzybowski, Andrzej

doi:10.2174/1381612822666161208094841

Cited by 9 publications

(3 citation statements)

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“…At present, most people believe dry eye is a type of inflammatory immune disease. The instability of tears can be caused by different mechanisms, causing ocular surface damage in dry eye patients 2 . The increased tear osmotic pressure caused by excessive evaporation of tears on the ocular surface is considered one of the contributors as well.…”

Section: Introductionmentioning

confidence: 99%

Air pollutant particulate matter 2.5 induces dry eye syndrome in mice

Tan

Yang

et al. 2018

Sci Rep

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In this study, we explored the effects of particulate matter 2.5 (PM2.5) eye drops on the ocular surface structure and tear function in mice and established a novel animal model for dry eye research. We found that, following treatment with PM2.5, the tear volume and, the tear film break-up time showed statistical differences at each time point (P < 0.05). The FL score of the PM2.5-treated group was higher than that of others (P < 0.05). The average number of corneal epithelial layer cells in groups A and B was significantly lower than that in group C (P < 0.05). Scanning electron microscopy and transmission electron microscopy revealed that the number of corneal epithelial microvilli and corneal desmosomes was drastically reduced in group C. PM2.5 induced apoptosis in the corneal superficial and basal epithelium and led to abnormal differentiation and proliferation of the ocular surface with higher expression levels of Ki67 and a reduced number of goblet cells in the conjunctival fornix in group C. PM2.5 significantly increased the levels of TNF-α, NF-κB p65 (phospho S536), and NF-κB in the cornea. Thus, the topical administration of PM2.5 in mice induces ocular surface changes that are similar to those of dry eye in humans, representing a novel model of dry eye.

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Section: Introductionmentioning

confidence: 99%

Air pollutant particulate matter 2.5 induces dry eye syndrome in mice

Tan

Yang

et al. 2018

Sci Rep

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“… 66 TRPV1 activation in response to hyperosmotic conditions has also been specifically studied in human corneal epithelial cells. 70 As a hyperosmotic environment is a common feature of DE, 71 TRPV1 channels may play an important role in the development and maintenance of the ocular pain experienced in DE. Upregulation of TRPV1 has been described in DE, interstitial cystitis, 72 and animal studies of fibromyalgia, 73 and it may play a role in mediating excitatory responses to the inflammatory mediators associated with DE symptoms.…”

Section: Potential Mechanisms Of Pain Processing Disorders: Peripheramentioning

confidence: 99%

Evidence that dry eye represents a chronic overlapping pain condition

et al. 2017

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Recent data suggest that corneal somatosensory dysfunction may be the underlying cause of severe dry eye symptoms in the absence of ocular surface pathology seen in a subset of patients diagnosed with “dry eye syndrome.” This subset of patients tends to demonstrate a unique constellation of symptoms that are persistent, more severe, and generally respond poorly to current dry eye therapies targeting inadequate or dysfunctional tears. A growing body of literature suggests that symptoms in these patients may be better characterized as neuropathic ocular pain rather than dry eye. In these patients, dry eye symptoms are often associated with numerous comorbid pain conditions and evidence of central pain processing abnormalities, where eye pain is just one of multiple overlapping peripheral manifestations. In this review, we discuss the concept and potential mechanisms of chronic overlapping pain conditions as well as evidence for considering neuropathic ocular pain as one of these overlapping pain conditions.

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“…Among the tear-mucin secretagogues two were evaluated in multiple preclinical models of aqueous deficient dry eye and have been launched in Japan. These include Mucosta® (rebamipide, Otsuka Pharmaceuticals) a novel quinolone derivative and Diquas® (diquafasol, Santen) a purinergic agonist (62). Rebamipide, whose detailed mechanism of action is not fully understood, has been shown to have mucosal protective properties, promote re-epithelialization of damaged tissue, and plays a role in inflammation resolution.…”

Section: Introductionmentioning

confidence: 99%

Translational Preclinical Pharmacologic Disease Models for Ophthalmic Drug Development

et al. 2019

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Preclinical models of human diseases are critical to our understanding of disease etiology, pathology, and progression and enable the development of effective treatments. An ideal model of human disease should capture anatomical features and pathophysiological mechanisms, mimic the progression pattern, and should be amenable to evaluating translational endpoints and treatment approaches. Preclinical animal models have been developed for a variety of human ophthalmological diseases to mirror disease mechanisms, location of the affected region in the eye and severity. These models offer clues to aid in our fundamental understanding of disease pathogenesis and enable progression of new therapies to clinical development by providing an opportunity to gain proof of concept (POC). Here, we review preclinical animal models associated with development of new therapies for diseases of the ocular surface, glaucoma, presbyopia, and retinal diseases, including diabetic retinopathy and age-related macular degeneration (AMD). We have focused on summarizing the models critical to new drug development and described the translational features of the models that contributed to our understanding of disease pathogenesis and establishment of preclinical POC.

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Hot Topics in Dry Eye Disease

Abstract: The focus of the management of DED has been taken away from just reducing symptoms and redirected towards specific targets of its physiopathology, being inflammation the most addressed topic.

Cited by 9 publications

References 0 publications

Air pollutant particulate matter 2.5 induces dry eye syndrome in mice

Air pollutant particulate matter 2.5 induces dry eye syndrome in mice

Evidence that dry eye represents a chronic overlapping pain condition

Translational Preclinical Pharmacologic Disease Models for Ophthalmic Drug Development

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