Allergic conjunctivitis future or investigational therapies: Difference between revisions
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(/* Mapracorat{{cite journal| author=Baiula M, Spartà A, Bedini A, Carbonari G, Bucolo C, Ward KW | display-authors=etal| title=Eosinophil as a cellular target of the ocular anti-allergic action of mapracorat, a novel selective glucocorticoid receptor agonist. | journal=Mol Vis | year= 2011 | volume= 17 | issue= | pages= 3208-23 | pmid=22194647 | doi= | pmc=3244483 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2219...) |
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* Others [[calcineurin]] inhibitors that appears to be well tolerated by patients with severe [[atopic]] [[blepharoconjunctivitis]]<ref name="pmid16965503">{{cite journal| author=Virtanen HM, Reitamo S, Kari M, Kari O| title=Effect of 0.03% tacrolimus ointment on conjunctival cytology in patients with severe atopic blepharoconjunctivitis: a retrospective study. | journal=Acta Ophthalmol Scand | year= 2006 | volume= 84 | issue= 5 | pages= 693-5 | pmid=16965503 | doi=10.1111/j.1600-0420.2006.00699.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16965503 }} </ref> and severe [[atopic]] [[keratoconjunctivitis]] are [[tacrolimus]] and [[pimecrolimus]]<ref name="pmid12464150">{{cite journal| author=Reynolds NJ, Al-Daraji WI| title=Calcineurin inhibitors and sirolimus: mechanisms of action and applications in dermatology. | journal=Clin Exp Dermatol | year= 2002 | volume= 27 | issue= 7 | pages= 555-61 | pmid=12464150 | doi=10.1046/j.1365-2230.2002.01148.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12464150 }} </ref>. | * Others [[calcineurin]] inhibitors that appears to be well tolerated by patients with severe [[atopic]] [[blepharoconjunctivitis]]<ref name="pmid16965503">{{cite journal| author=Virtanen HM, Reitamo S, Kari M, Kari O| title=Effect of 0.03% tacrolimus ointment on conjunctival cytology in patients with severe atopic blepharoconjunctivitis: a retrospective study. | journal=Acta Ophthalmol Scand | year= 2006 | volume= 84 | issue= 5 | pages= 693-5 | pmid=16965503 | doi=10.1111/j.1600-0420.2006.00699.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16965503 }} </ref> and severe [[atopic]] [[keratoconjunctivitis]] are [[tacrolimus]] and [[pimecrolimus]]<ref name="pmid12464150">{{cite journal| author=Reynolds NJ, Al-Daraji WI| title=Calcineurin inhibitors and sirolimus: mechanisms of action and applications in dermatology. | journal=Clin Exp Dermatol | year= 2002 | volume= 27 | issue= 7 | pages= 555-61 | pmid=12464150 | doi=10.1046/j.1365-2230.2002.01148.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12464150 }} </ref>. | ||
===Mapracorat<ref name="pmid22194647">{{cite journal| author=Baiula M, Spartà A, Bedini A, Carbonari G, Bucolo C, Ward KW | display-authors=etal| title=Eosinophil as a cellular target of the ocular anti-allergic action of mapracorat, a novel selective glucocorticoid receptor agonist. | journal=Mol Vis | year= 2011 | volume= 17 | issue= | pages= 3208-23 | pmid=22194647 | doi= | pmc=3244483 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22194647 }} </ref>=== | ===Mapracorat<ref name="pmid22194647">{{cite journal| author=Baiula M, Spartà A, Bedini A, Carbonari G, Bucolo C, Ward KW | display-authors=etal| title=Eosinophil as a cellular target of the ocular anti-allergic action of mapracorat, a novel selective glucocorticoid receptor agonist. | journal=Mol Vis | year= 2011 | volume= 17 | issue= | pages= 3208-23 | pmid=22194647 | doi= | pmc=3244483 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22194647 }} </ref>=== | ||
*Mapracorat is a novel selective [[agonist]] of the [[glucocorticoid]] receptor, resulting in a lower potential for side effect. | |||
*In vitro, it inhibited migration and [[IL-8]] release from [[eosinophils]] and the secretion of [[IL-6]], [[IL-8]], [[CCL5]]/[[RANTES]], and [[TNF-α]] from a human mast [[cell]] line with equal [[potency]] as [[dexamethasone]], but it was less potent in inducing [[annexin]] I and [[CXCR4]] expression on the human [[eosinophils]]. | |||
*Animal model of [[allergic]] [[conjunctivitis]] demonstrated mapracorat was similar to [[dexamethasone]] [[eye]] drops in analogous reduction of [[clinical]] [[symptoms]] and [[conjunctival]] [[eosinophil]]. Hence,studies suggest this compound as a candidate for [[clinical]] trials of [[ocular]] [[allergy]]. | |||
==References== | ==References== | ||
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Overview
Future or Investigational therapies
Calcineurin inhibitors
- They are capable of inducing local immunosuppression by blocking Th2 lymphocyte proliferation and IL-2 production and reducing eosinophils via inhibition of IL-5.
- Topical [1] and systemic cyclosporine a (CsA) [2] have been suggested in the treatment of severe atopic keratoconjunctivitis.
- Use of CsA appears to be safe and can eliminate the need/dependence of steroids.
- Others calcineurin inhibitors that appears to be well tolerated by patients with severe atopic blepharoconjunctivitis[3] and severe atopic keratoconjunctivitis are tacrolimus and pimecrolimus[4].
Mapracorat[5]
- Mapracorat is a novel selective agonist of the glucocorticoid receptor, resulting in a lower potential for side effect.
- In vitro, it inhibited migration and IL-8 release from eosinophils and the secretion of IL-6, IL-8, CCL5/RANTES, and TNF-α from a human mast cell line with equal potency as dexamethasone, but it was less potent in inducing annexin I and CXCR4 expression on the human eosinophils.
- Animal model of allergic conjunctivitis demonstrated mapracorat was similar to dexamethasone eye drops in analogous reduction of clinical symptoms and conjunctival eosinophil. Hence,studies suggest this compound as a candidate for clinical trials of ocular allergy.
References
- ↑ Tzu JH, Utine CA, Stern ME, Akpek EK (2012). "Topical calcineurin inhibitors in the treatment of steroid-dependent atopic keratoconjunctivitis". Cornea. 31 (6): 649–54. doi:10.1097/ICO.0b013e31822481c2. PMID 22378107.
- ↑ Cornish KS, Gregory ME, Ramaesh K (2010). "Systemic cyclosporin A in severe atopic keratoconjunctivitis". Eur J Ophthalmol. 20 (5): 844–51. doi:10.1177/112067211002000506. PMID 20491051.
- ↑ Virtanen HM, Reitamo S, Kari M, Kari O (2006). "Effect of 0.03% tacrolimus ointment on conjunctival cytology in patients with severe atopic blepharoconjunctivitis: a retrospective study". Acta Ophthalmol Scand. 84 (5): 693–5. doi:10.1111/j.1600-0420.2006.00699.x. PMID 16965503.
- ↑ Reynolds NJ, Al-Daraji WI (2002). "Calcineurin inhibitors and sirolimus: mechanisms of action and applications in dermatology". Clin Exp Dermatol. 27 (7): 555–61. doi:10.1046/j.1365-2230.2002.01148.x. PMID 12464150.
- ↑ Baiula M, Spartà A, Bedini A, Carbonari G, Bucolo C, Ward KW; et al. (2011). "Eosinophil as a cellular target of the ocular anti-allergic action of mapracorat, a novel selective glucocorticoid receptor agonist". Mol Vis. 17: 3208–23. PMC 3244483. PMID 22194647.