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      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

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      Anti-platelet effects of anti-glaucomatous eye drops: an in vitro study on human platelets

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          Abstract

          Purpose

          Altered platelet aggregability has been implicated in the pathogenesis of glaucoma. This study aims to investigate the anti-platelet potential of intraocular pressure lowering drops, with the possibility of establishing it as an additional mechanism of anti-glaucomatous action.

          Materials and methods

          The anti-aggregating effects of a series of anti-glaucomatous eye drops were determined on human platelets in the platelet aggregation model, using four known aggregating factors (platelet activating factor [PAF], adenosine diphosphate [ADP], thrombin receptor-activating peptide [TRAP], and arachidonic acid [AA]).

          Results

          Almost all of the tested samples inhibited platelet aggregation induced by PAF, ADP, TRAP, and AA, except for Alphagan, which did not demonstrate inhibition of ADP- and TRAP-induced aggregation at a wide range of concentrations. Trusopt, Betoptic, and Azarga eye drops were the most potent inhibitors of all four aggregating factors, while Alphagan was the least potent ( P<0.05).

          Conclusion

          This study shows that anti-glaucomatous eye drops possess anti-platelet effects, and this was shown for the first time by experimenting on human platelets.

          Most cited references33

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          Current concepts in the pathophysiology of glaucoma

          Renu Agarwal, Suresh Gupta, Puneet Agarwal … (2009)
          Glaucoma, the second leading cause of blindness, is characterized by changes in the optic disc and visual field defects. The elevated intraocular pressure was considered the prime factor responsible for the glaucomatous optic neuropathy involving death of retinal ganglion cells and their axons. Extensive investigations into the pathophysiology of glaucoma now reveal the role of multiple factors in the development of retinal ganglion cell death. A better understanding of the pathophysiological mechanisms involved in the onset and progression of glaucomatous optic neuropathy is crucial in the development of better therapeutic options. This review is an effort to summarize the current concepts in the pathophysiology of glaucoma so that newer therapeutic targets can be recognized. The literature available in the National Medical Library and online Pubmed search engine was used for literature review.
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            Platelet-activating factor. Evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators).

            C Demopoulos, R N Pinckard, D J Hanahan (1979)
            A glyceryl ether containing phosphoglyceride, 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (Ac-GEPC), has been shown to have a biological activity indistinguishable from that of naturally generated (rabbit) platelet activating factor (PAF). Its biochemical and biological properties so closely parallel those of naturally occurring PAF that we propose they are one and the same compound. Both PAF and AcGEPC could be converted to an inactive form through base-catalyzed methanolysis and restored to 100% functional activity by reaction with acetic anhydride. The synthetic lipid, AcGEPC, elicited 50% secretion of serotonin from rabbit platelets at a level of 10(-10) M (based on phosphorus). A propionyl derivative had somewhat comparable activity towards platelets, whereas the butyryl homologue was some 7-fold less active and the stearoyl derivative was inactive. These short chain acylglyceryl ether phosphoglycerides represent an entirely new, potent and unique class of lipid chemical mediators. 1-Acyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (AcLL) also exhibited activity towards platelets but was some 200-fold less active than AcGepc. the propionyl lysolecithin behaved quite similarly to AcLL, but butyryl and stearoyl lysolecithins showed no activity.
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              Detection and prognostic significance of optic disc hemorrhages during the Ocular Hypertension Treatment Study.

              W Feuer, Elizabeth Kass, J Piltz … (2006)
              To compare the rates of detection of optic disc hemorrhages by clinical examination and by review of optic disc photographs at the Optic Disc Reading Center (ODRC), to assess the incidence of and the predictive factors for disc hemorrhages in the annual disc photographs of the Ocular Hypertension Treatment Study (OHTS), and to determine whether optic disc hemorrhages predict the development of primary open-angle glaucoma (POAG) in the OHTS. Cohort study. Three thousand two hundred thirty-six eyes of 1618 participants. Both eyes of participants were examined for optic disc hemorrhages every 6 months by clinical examination, with dilated fundus examinations every 12 months, and by annual review of stereoscopic disc photographs at the ODRC. Incidence of optic disc hemorrhages and POAG end points. Median follow-up was 96.3 months. Stereophotography-confirmed glaucomatous optic disc hemorrhages were detected in 128 eyes of 123 participants before the POAG end point. Twenty-one cases (16%) were detected by both clinical examination and review of photographs, and 107 cases (84%) were detected only by review of photographs (P<0.0001). Baseline factors associated with disc hemorrhages were older age, thinner corneas, larger vertical cup-to-disc ratio, larger pattern standard deviation index on perimetry, family history of glaucoma, and smoking status. The occurrence of a disc hemorrhage increased the risk of developing POAG 6-fold in a univariate analysis (P<0.001; 95% confidence interval, 3.6-10.1) and 3.7-fold in a multivariate analysis that included baseline factors predictive of POAG (P<0.001; 95% confidence interval, 2.1-6.6). The 96-month cumulative incidence of POAG in the eyes without optic disc hemorrhage was 5.2%, compared with 13.6% in the eyes with optic disc hemorrhage. In eyes with a disc hemorrhage in which a POAG end point developed, the median time between the 2 events was 13 months. Review of stereophotographs was more sensitive at detecting optic disc hemorrhage than clinical examination. The occurrence of an optic disc hemorrhage was associated with an increased risk of developing a POAG end point in participants in the OHTS. However, most eyes (86.7%) in which a disc hemorrhage developed have not experienced a POAG end point to date.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): Drug Design, Development and Therapy
                Title: Drug Design, Development and Therapy
                Publisher: Dove Medical Press
                ISSN (Electronic): 1177-8881
                Publication date Collection: 2017
                Publication date (Electronic): 19 April 2017
                Volume: 11
                Pages: 1267-1272
                Affiliations
                [1 ]1st Department of Ophthalmology, Medical School, University of Athens, Athens, Greece
                [2 ]Biomedical Research Foundation, Academy of Athens, Athens, Greece
                [3 ]Laboratory of Biology, Biochemistry, Physiology and Microbiology, Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
                [4 ]Royal Eye Infirmary, Dorset County Hospital NHS Foundation Trust, Dorchester, UK
                Author notes
                Correspondence: Marilita M Moschos, 1st Department of Ophthalmology, University of Athens, 6 Ikarias Street, 14578, Ekali, Athens, Attica, Greece, Tel +30 69 4488 7319, Fax +30 21 0412 2139, Email moschosmarilita@ 123456yahoo.fr
                Article
                Publisher ID: dddt-11-1267
                DOI: 10.2147/DDDT.S131582
                PMC ID: 5402915
                SO-VID: 71c3eb0a-9f53-42cd-8a7e-ade47f5a2981
                Copyright © © 2017 Moschos et al. This work is published and licensed by Dove Medical Press Limited
                License:

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed

                History
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: glaucoma,eye,platelet,aggregation,paf,trap
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: glaucoma, eye, platelet, aggregation, paf, trap

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