P2Y2 receptor agonists for the treatment of dry eye disease: a review

Lau, Oliver C.F.; Samarawickrama, Chameen; Skalicky, Simon E.

doi:10.2147/opth.s39699

Cited by 37 publications

(28 citation statements)

References 45 publications

(75 reference statements)

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“… 2 , 3 , 30 In addition, the diquafosol eye drops probably increased water secretion, 8 whereas rebamipide eye drops had anti-inflammatory effects 11 , 12 on these types of immune-mediated dry eye. 31 …”

Section: Discussionmentioning

confidence: 99%

Long-term Rebamipide and Diquafosol in Two Cases of Immune-Mediated Dry Eye

Yamane¹,

Ogawa²,

Fukui³

et al. 2015

Optometry and Vision Science

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Section: Discussionmentioning

confidence: 99%

Long-term Rebamipide and Diquafosol in Two Cases of Immune-Mediated Dry Eye

Yamane¹,

Ogawa²,

Fukui³

et al. 2015

Optometry and Vision Science

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“…Treatment for dry eye by a long lasting P2Y 2 R agonist, diquafosol, was developed by Inspire Pharmaceuticals, Inc. and is currently in use in Japan and Korea (see Lau et al, 2014 ).…”

Section: Diseases Of the Special Sensesmentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

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“…Furthermore, purinergic receptor P2Y, G-protein coupled, 2 ( P2RY2 ), which harbored the 12 th ranked associated SNP (rs7111814) in this study, is also linked to dry eye syndrome through its role in regulation of mucin secretion at the ocular surface [ 20 - 21 ] . Recently, an agonist of P2Y2 receptor (diquafosol) was developed as a new pharmacologic agent for dry eye disease [ 20 ] . In addition, B3GNT4 , which was the most strongly associated locus in the present study, shows glycosyl transferase activity that helps to regulate the formation of mucin by O -glycosylation [ 22 ] .…”

Section: Discussionmentioning

confidence: 99%

A pilot exome-wide association study of age-related cataract in Koreans

et al. 2016

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Age-related cataract (ARC) is the most common cause of visual impairment and blindness worldwide. A previous study reported that genetic factors could explain approximately 50% of the heritability of cataract. However, a genetic predisposition to ARC and the contributing factors have not yet been elucidated in the Korean population. In this study, we assessed the influence of genetic polymorphisms on the risk of ARC in Koreans, including 156 cataract cases and 138 healthy adults. We conducted an exome-wide association study using Illumina Human Exome-12v1.2 platform to screen 244,770 single nucleotide polymorphisms (SNPs). No SNPs reached exome-wide significance level of association (P < 1×10−6). B3GNT4 rs7136356 showed the most significant association with ARC (P = 6.54×10−5). Two loci (MUC16 and P2RY2) among the top 20 ARC-associated SNPs were recognized as probably linked to cataractogenesis. Functions of these genes were potentially related to regulating dehydration or homeostasis of the eyes, and showed a potential association with dry eye disease. This finding suggests that mucin- and dry eye disease-related genes may play a significant role in cataractogenesis. Our study provides insight into the genetic predisposition of ARC in Koreans. Additional studies with larger sample sizes are required to confirm the results of this study.

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P2Y2 receptor agonists for the treatment of dry eye disease: a review

Cited by 37 publications

References 45 publications

Long-term Rebamipide and Diquafosol in Two Cases of Immune-Mediated Dry Eye

Long-term Rebamipide and Diquafosol in Two Cases of Immune-Mediated Dry Eye

Purinergic Signalling: Therapeutic Developments

A pilot exome-wide association study of age-related cataract in Koreans

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