June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Effects of tafluprost on endothelin-1-induced retinal injury in the rat
Author Affiliations & Notes
  • Atsushi Nagata
    Ophthalmology, Kanazawa Medical Center, Kanazawa-shi, Japan
    Ophthalmology and Visual Science, Kanazawa University Graduate School of Medical Science, Kanazawa-shi, Japan
  • Katsumi Oomachi
    Research and Development Division, Santen Pharmaceutical Co. Ltd., Ikoma-shi, Japan
  • Tomomi Higashide
    Ophthalmology and Visual Science, Kanazawa University Graduate School of Medical Science, Kanazawa-shi, Japan
  • Satoshi Shirae
    Research and Development Division, Santen Pharmaceutical Co. Ltd., Ikoma-shi, Japan
  • Masatsugu Nakamura
    Research and Development Division, Santen Pharmaceutical Co. Ltd., Ikoma-shi, Japan
  • Atsushi Shimazaki
    Research and Development Division, Santen Pharmaceutical Co. Ltd., Ikoma-shi, Japan
  • Naruhiro Ishida
    Research and Development Division, Santen Pharmaceutical Co. Ltd., Ikoma-shi, Japan
  • Kazuhisa Sugiyama
    Ophthalmology and Visual Science, Kanazawa University Graduate School of Medical Science, Kanazawa-shi, Japan
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 429. doi:
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      Atsushi Nagata, Katsumi Oomachi, Tomomi Higashide, Satoshi Shirae, Masatsugu Nakamura, Atsushi Shimazaki, Naruhiro Ishida, Kazuhisa Sugiyama; Effects of tafluprost on endothelin-1-induced retinal injury in the rat. Invest. Ophthalmol. Vis. Sci. 2013;54(15):429.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To examine neuroprotective effect of tafluprost on endothelin-1 (ET-1)-induced retinal injury in the rat.

Methods: Male Brown-Norway rats, 10 weeks of age and weighing 200 to 250 g, were used in the study. An intravitreal injection of ET-1 (20 pmol/eye) was performed in one eye of each rat, which was followed by topical administration of tafluprost eye drops (n=12) or saline (n=12) once daily for 4 weeks in a double blind fashion. An experimental optical coherence tomography (OCT) system was used which was optimized to acquire retinal images in rat fundus (Nagata A, et al. IOVS 2009). Cross-sectional OCT imaging was performed in a circumpapillary fashion, with a circle diameter of 1000 µm centered on the optic disc 1, 2, 4 weeks after the ET-1 injection under general anesthesia with intraperitoneal pentobarbital. The retinal nerve fiber layer (RNFL) thickness and inner retinal thickness (from RNFL to inner nuclear layer) was measured. Afterwards RGCs were retrogradely labeled with fluorogold which was applied to the superior colliculus. Seven days later, the rats were euthanatized, and their retinas were prepared as flatmounts for examination under fluorescence microscopy to estimate RGC survival.

Results: Since two rats treated with saline died during the experimental period, they were excluded. In both groups, RNFL thickness was increased 1 week after the ET-1 injection (p<0.01), but then decreased significantly at the fourth week (p<0.01). In both groups, inner retinal thickness progressively decreased after the second week (baseline vs. 2weeks, p<0.01; baseline vs. 4 weeks, p<0.001). Thickness of RNFL and inner retina in eyes treated with tafluprost was significantly thicker than that in eyes treated with saline (RNFL, p=0.021; inner retina, p=0.046, two-way repeated ANOVA). The average number of RGCs in the central retina of eyes treated with tafluprost was significantly greater than that of eyes treated with saline (2411±213 vs. 2101±397 cells/mm2, p=0.03).

Conclusions: Treatment with topical tafluprost reduced the thinning of the inner retinal thickness and RGC loss caused by intravitreal ET-1 injection when compared to saline instillation. Repeated topical administration of tafluprost may be protective against the ET-1-induced retinal injury in the rat.

Keywords: 503 drug toxicity/drug effects • 615 neuroprotection • 551 imaging/image analysis: non-clinical  
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