Emerging Therapeutics for Ocular Surface Disease

Bielory, Leonard; Schoenberg, Dovid

doi:10.1007/s11882-019-0844-8

Cited by 26 publications

(19 citation statements)

References 64 publications

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“…Ocular allergy occurs through activation of Th2 cell-mediated cascades, leading to production of IgE; it can also occur in combination with T lymphocyte-mediated disorders, with subsequent development of acute and chronic forms of ocular allergy. This proinflammatory state caused by activation of transcription factors creates an immune cascade via increased cellular infiltration (e.g., eosinophils) and secretion of chemokines, cytokines, and metalloproteinases, which further promotes ocular surface damage and disruption of epithelial barriers [147].…”

Section: Lts and Allergic Diseasesmentioning

confidence: 99%

“…There are limited approved therapeutic options for treatment of allergic conjunctivitis. Of interest, it was confirmed that the nonpharmacological interventions of artificial tears and the use of cold compresses alone or in combination often provide patients with significant benefits [147]. In the area of pharmacotherapy, there has been one new approval of an antihistamine, cetirizine.…”

Section: Lts and Allergic Diseasesmentioning

confidence: 99%

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The Role of Leukotrienes as Potential Therapeutic Targets in Allergic Disorders

Jo-Watanabe

Okuno

Yokomizo

2019

IJMS

104

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Leukotrienes (LTs) are lipid mediators that play pivotal roles in acute and chronic inflammation and allergic diseases. They exert their biological effects by binding to specific G-protein-coupled receptors. Each LT receptor subtype exhibits unique functions and expression patterns. LTs play roles in various allergic diseases, including asthma (neutrophilic asthma and aspirin-sensitive asthma), allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and anaphylaxis. This review summarizes the biology of LTs and their receptors, recent developments in the area of anti-LT strategies (in settings such as ongoing clinical studies), and prospects for future therapeutic applications.

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Section: Lts and Allergic Diseasesmentioning

confidence: 99%

Section: Lts and Allergic Diseasesmentioning

confidence: 99%

The Role of Leukotrienes as Potential Therapeutic Targets in Allergic Disorders

Jo-Watanabe

Okuno

Yokomizo

2019

IJMS

104

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“…Although IL‐1R signaling promotes ocular surface inflammation and mucin acidification in the context of dry eye diseases (52), we could not find prior evidence for a role in homeostasis of surface glycosylation at the ocular surface or elsewhere. Given the potential use of IL‐1R antagonists in the management of dry eye and other ocular surface inflammatory diseases (52–54), the notion that IL‐1R affects ocular surface homeostasis warrants further investigation. Considering the blotting procedure removes more than just the cell glycocalyx, other methods will need to be used to study how IL‐1R regulates corneal surface glycosylation at the molecular level.…”

Section: Resultsmentioning

confidence: 99%

Corneal surface glycosylation is modulated by IL‐1R and Pseudomonas aeruginosa challenge but is insufficient for inhibiting bacterial binding

Jolly¹,

Agarwal²,

Metruccio³

et al. 2017

FASEB j.

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Cell surface glycosylation is thought to be involved in barrier function against microbes at mucosal surfaces. Previously we showed that the epithelium of healthy mouse corneas becomes vulnerable to adhesion if it lacks the innate defense protein MyD88 (myeloid differentiation primary response gene 88), or after superficial injury by blotting with tissue paper. Here we explored their effect on corneal surface glycosylation using a metabolic label, tetra-acetylated-azidoacetylgalactosamine (AcGalNAz). AcGalNAz treatment labeled the surface of healthy mouse corneas, leaving most cells viable, and bacteria preferentially associated with GalNAz-labeled regions. Surprisingly, corneas from MyD88 mice displayed similar GalNAz labeling to wild-type corneas, but labeling was reduced and patchy on IL-1 receptor (IL-1R)-knockout mouse corneas ( < 0.05, ANOVA). Tissue paper blotting removed GalNAz-labeled surface cells, causing DAPI labeling (permeabilization) of underlying cells. MS of material collected on the tissue paper blots revealed 67 GalNAz-labeled proteins, including intracellular proteins. These data show that the normal distribution of surface glycosylation requires IL-1R, but not MyD88, and is not sufficient to prevent bacterial binding. They also suggest increased adhesion to MyD88 and blotted corneas is not due to reduction in total surface glycosylation, and for tissue paper blotting is likely due to cell permeabilization.-Jolly, A. L., Agarwal, P., Metruccio, M. M. E., Spiciarich, D. R., Evans, D. J., Bertozzi, C. R., Fleiszig, S. M. J. Corneal surface glycosylation is modulated by IL-1R and challenge but is insufficient for inhibiting bacterial binding.

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“…Examples include loratadine, desloratadine, and fexofenadine. More recently, known potent oral antihistamines, cetirizine and bilastine, have been formulated for ophthalmic use and are showing promise for AC treatment [ 97 ]. Bilastine, for example, is a well-established second-generation oral antihistamine commonly used in allergic disorders.…”

Section: Current Treatment Approachesmentioning

confidence: 99%

Therapeutic Targets in Allergic Conjunctivitis

Labib

Chigbu

2022

Pharmaceuticals

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Allergic conjunctivitis (AC) is a common condition resulting from exposure to allergens such as pollen, animal dander, or mold. It is typically mediated by allergen-induced crosslinking of immunoglobulin E attached to receptors on primed conjunctival mast cells, which results in mast cell degranulation and histamine release, as well as the release of lipid mediators, cytokines, and chemokines. The clinical result is conjunctival hyperemia, tearing, intense itching, and chemosis. Refractory and chronic cases can result in ocular surface complications that may be vision threatening. Patients who experience even mild forms of this disease report an impact on their quality of life. Current treatment options range from non-pharmacologic therapies to ocular and systemic options. However, to adequately control AC, the use of multiple agents is often required. As such, a precise understanding of the immune mechanisms responsible for this ocular surface inflammation is needed to support ongoing research for potential therapeutic targets such as chemokine receptors, cytokine receptors, non-receptor tyrosine kinases, and integrins. This review utilized several published articles regarding the current therapeutic options to treat AC, as well as the pathological and immune mechanisms relevant to AC. This review will also focus on cellular and molecular targets in AC, with particular emphasis on potential therapeutic agents that can attenuate the pathology and immune mechanisms driven by cells, receptors, and molecules that participate in the immunopathogenesis and immunopathology of AC.

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Emerging Therapeutics for Ocular Surface Disease

Cited by 26 publications

References 64 publications

The Role of Leukotrienes as Potential Therapeutic Targets in Allergic Disorders

The Role of Leukotrienes as Potential Therapeutic Targets in Allergic Disorders

Corneal surface glycosylation is modulated by IL‐1R and Pseudomonas aeruginosa challenge but is insufficient for inhibiting bacterial binding

Therapeutic Targets in Allergic Conjunctivitis

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