Effects of prostaglandin F2α analogues on endothelin-1-induced impairment of rabbit ocular blood flow: Comparison among tafluprost, travoprost, and latanoprost

We investigated the effects of prostaglandin F2α (PGF2α) analogues on the endothelin-1 (ET-1)-induced impairment of optic nerve head (ONH) blood flow and on ET-1-induced contraction in isolated ciliary artery segments. In male rabbits, one of four PGF2α analogues [0.0015% tafluprost, 0.0015% 15-hydroxyl tafluprost (15-OH tafluprost), 0.005% latanoprost, or 0.004% travoprost] was topically administered at various pretreatment times before intravitreal ET-1 injection. ONH blood flow was estimated by the laser speckle method, which expresses blood velocity as a quantitative index, the squared blur rate (SBR). SBR was measured just before (baseline value) and at 30, 60, and 120 min after ET-1 injection. SBR was significantly decreased from 4.47 ± 0.20 to 3.50 ± 0.10 (78.6 ± 2.4% of baseline) at 120 min after intravitreal ET-1 injection (5 pmol/eye). The ET-1-induced decrease was almost completely prevented by tafluprost and significantly inhibited by the other three analogues. The inhibitory effect lasted longest with tafluprost, as indicated by the effective pretreatment times (tafluprost: 90, 120, or 240 min; 15-OH tafluprost: 90, but not 120 or 240 min; latanoprost and travoprost: 120, but not 240 min). In vitro, the effects of PGF2α analogues on ET-1-induced contractions in male rabbit ciliary arteries were evaluated using an isometric tension recording system. Tafluprost, latanoprost, travoprost, and 15-OH tafluprost concentration-dependently relaxed the 10 nM ET-1-induced ciliary artery contraction. Improvement of the ocular circulation may be superior with tafluprost than with the other PGF2α analogues. The underlying mechanism may involve relaxation of ocular resistance vessels.

Research highlights
► Present study is the first to report that topical administration of PGF2α analogues (tafluprost, latanoprost, travoprost) inhibit the ET-1-induced impairment of ONH blood flow in rabbit.
► PGF2α analogues (tafluprost, latanoprost, travoprost) relaxed rabbit isolated ciliary artery segments precontracted by ET-1 in vitro, and it suggests that pretreatment with PGF2α analogues inhibits the ET-1-induced impairment of ONH blood flow via a mechanism that may involve relaxation of ocular arterial vessels.
► Since the inhibitory effect of tafluprost on the ET-1-induced decrease in ONH blood flow was more prolonged than those of 15-OH tafluprost, travoprost, and latanoprost, the presence of di-fluorine at the carbon 15 position may contribute to the longer-lasting nature of this inhibitory effect of tafluprost. These results suggest that as regards ocular circulation improvement, tafluprost may be superior to other PGF2α analogues.