endothelin-1 and tafluprost

To determine whether optical coherence tomography (OCT) is a useful technique to monitor retinal damage and to evaluate the neuroprotective effect of topical tafluprost in a rat model of intravitreal endothelin-1 (ET-1) injection.. A single intravitreal injection of ET-1 (0.2-200 pmol/eye) was performed in one eye. Optical coherence tomography imaging was performed until 2 weeks after ET-1 injection. Subsequently, an intravitreal injection of ET-1 (20 pmol/eye) was performed in one eye of each rat, which was followed by topical instillation of tafluprost or saline once daily for 4 weeks. Optical coherence tomography imaging was performed until 4 weeks after ET-1 injection. After the last OCT session, retinal ganglion cells (RGCs) were retrogradely labeled with Fluorogold.. Endothelin-1 at doses of 20 to 200 pmol/eye caused a significant decrease in inner retinal thickness, whereas ET-1 at doses of 0.2 to 5 pmol/eye did not. The inner retinal thickness at 2 weeks postinjection was strongly correlated with Fluorogold-labeled RGC counts in the central retina (r = 0.92, P < 0.001). The inner retina of eyes treated with tafluprost was significantly thicker than eyes treated with saline at 1 and 2 weeks (P = 0.038 and P = 0.045, respectively). Fluorogold-labeled RGC counts in the central retina of eyes treated with tafluprost were significantly greater than in eyes treated with saline (P = 0.03).. Optical coherence tomography is useful for monitoring inner retinal damage in a rat model of intravitreal ET-1 injection. Daily topical administration of tafluprost may be protective against ET-1-induced retinal injury in the rat.

Topics: Animals; Axons; Cell Count; Endothelin-1; Intravitreal Injections; Male; Neuroprotective Agents; Prostaglandins F; Rats; Rats, Inbred BN; Retinal Diseases; Retinal Ganglion Cells; Tomography, Optical Coherence

We investigated the effects of prostaglandin F(2α) (PGF(2α)) 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 PGF(2α) 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 PGF(2α) 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 PGF(2α) analogues. The underlying mechanism may involve relaxation of ocular resistance vessels.

Topics: Administration, Topical; Animals; Antihypertensive Agents; Blood Flow Velocity; Ciliary Arteries; Cloprostenol; Dinoprost; Endothelin-1; Isometric Contraction; Laser-Doppler Flowmetry; Latanoprost; Male; Muscle, Smooth, Vascular; Optic Disk; Prostaglandins F; Prostaglandins F, Synthetic; Rabbits; Regional Blood Flow; Travoprost