Impact of prostaglandin glaucoma drops on platelet-activating factor action: an in vitro study

Abstract

AimThe aim of this study was to investigate the effect of different prostaglandin analogs on platelet-activating factor (PAF) levels.MethodsThree prostaglandin analogs were selected: bimatoprost 0.3 mg/mL, latanoprost 50 μg/mL, and tafluprost 15 μg/mL. Each drug sample was tested for its ability to cause platelet aggregation, which was measured as PAF-induced aggregation, before and after the addition of various concentrations of the examined sample, creating a linear curve of percentage inhibition (ranging from 0% to 100%) versus different concentrations of the sample. The concentration of the sample that inhibited 50% PAF-induced aggregation was calculated based on this curve, and this value was defined as IC50. In addition, the effect of eye drops on PAF metabolism was examined, through an in vitro analysis on PAF basic metabolic enzymes (PAF-cholinephosphotransferase, PAF-acetyl-CoA:1-O-alkyl-sn-glycero-3-phosphocholine acetyltransferase, and PAF-acetylhydrolase).ResultsThe IC50 values for Lumigan UD® (bimatoprost 0.3 mg/mL), Monoprost® (latanoprost 50 μg/mL), and Saflutan (tafluprost 15 μg/mL) were 8.7, 0.28, and 1.4 μg/mL, respectively.DiscussionAll three prostaglandin analogs suspended PAF, but bimatoprost induced the most potent inhibition, compared to tafluprost and to the weak effect of latanoprost.

Effect of Cromakalim Prodrug 1 (CKLP1) on Aqueous Humor Dynamics and Feasibility of Combination Therapy With Existing Ocular Hypotensive Agents

“…There is evidence of cytoskeletal modulation by rho kinase inhibitors, 76 whereas latanoprost has been shown to increase phosphoinositide turnover following binding with FP receptors in human trabecular meshwork and rat vascular smooth muscle cells. 77 – 79 Additionally, latanoprost can also affect platelet activity factor in rabbit blood 80 and endothelin receptors of human choroidal melanocytes. 81 A recently published study from our laboratory 82 has found that the IOP-lowering effect of latanoprost is mediated by signaling through stanniocalcin-1 (STC-1) and that STC-1 by itself can mimic the ocular hypotensive effect of latanoprost.…”

PAF‐induced inflammatory and immuno‐allergic ophthalmic diseases and their mitigation with PAF receptor antagonists: Cell and nuclear effects

“…Additional disease‐linkage studies showed that the expression of the PAF catabolic enzyme, PAF‐acetyl hydrolase (PAF‐AH), was significantly elevated in retinas of diabetic rats 106 . And, this seemed to translate to clinical studies since plasma PAF‐AH was also up‐regulated in diabetic patients with proliferative retinopathy 107 . However, whether these observations were causal or consequential of the disease remains to be determined.…”

“… 106 And, this seemed to translate to clinical studies since plasma PAF‐AH was also up‐regulated in diabetic patients with proliferative retinopathy. 107 However, whether these observations were causal or consequential of the disease remains to be determined. Nevertheless, PAF seems to be a contributor to the pathological milieu of factors and processes in retinal diseases and perhaps PAF receptor antagonist can have a role in mitigating some signs and symptoms associated with diabetic retinopathy, ROP and age‐related macular degeneration (AMD).…”