Yoshitaka Horikawa

Inhibitory effect of losartan on laser-induced choroidal neovascularization in rats

PURPOSE To investigate the inhibitory effects of losartan, an angiotensin receptor antagonist, on angiogenesis in a rat model of laser-induced choroidal neovascularization. METHODS Experimental study. Fifteen Brown-Norway male rats received losartan (approximately 5 mg/kg/d) in drinking water, and 15 Brown-Norway male rats received unsupplemented drinking water 1 week before photocoagulation, and it was continued to the end of the study. Two weeks after intense laser photocoagulation, choroidal neovascularization was evaluated by fluorescein angiography and histopathologic evaluation. RESULTS The incidence of choroidal neovascularization formation was 99.5 +/-.2% (mean +/- standard deviation) in controls and 72.5 +/- 8.8% in losartan-treated rats (P <.01). Quantitative morphometric assessment revealed mean choroidal neovascularization lesion thickness of 54 and 44.8 microm, respectively, in controls and losartan-treated rats (P <.01). CONCLUSION Losartan seems to inhibit development of laser-induced choroidal neovascularization. Angiotensin receptor antagonists may be useful as prophylaxis against choroidal neovascularization associated with age-related macular degeneration.

Detection of drusen in the fellow eye of Japanese patients with age-related macular degeneration using scanning laser ophthalmoscopy.

OBJECTIVE To study the prevalence of drusen in the fellow eye of Japanese patients with age-related macular degeneration (AMD). DESIGN Retrospective, cross-sectional study. PARTICIPANTS Seventeen eyes of 17 Japanese patients with unilateral AMD. MAIN OUTCOME MEASURES To compare the frequency of drusen based on photography and scanning laser ophthalmoscopy with confocal and ring apertures and a diode laser (780 nm). RESULTS Using the scanning laser ophthalmoscope (SLO) with a ring aperture, drusen were detected clearly as in topographic imaging. In the fellow eyes of the study patients with AMD, photography showed drusen in 10 cases (58.8%); however, SLO imaging detected drusen in 15 cases (88.2%). The number of drusen detected using SLO imaging was significantly greater than when using photography (P < 0.05). CONCLUSIONS Scanning laser ophthalmoscope imaging is superior to photography for detecting drusen in the fellow eyes of Japanese patients with unilateral AMD. The prevalence of drusen in the fellow eye of Japanese patients with AMD is much higher than previously speculated.

Inhibitory effect of bucillamine on laser-induced choroidal neovascularization in rats.

Purpose. We investigated the inhibitory effects of bucillamine on formation of laser-induced choroidal neovascularization (CNV) in a rat model. Methods. Bucillamine administration (approximately 150?mg/kg/day) was started 1 week before photocoagulation and continued to the end of the study. Control groups received drinking water. Two weeks after photocoagulation, choroidal neovascularization development was evaluated using simultaneous fluorescein and indocyanine green angiography, and the maximal thickness of the lesions was measured histologically. Results. The incidence of CNV formation was 99.5 ± 0.2% [mean ± standard deviation (SD)] in control rats and 64.3 ± 15.1% with bucillamine (P < 0.01). Histological study showed that the thickness of the CNV lesions was 23.4 ± 6.5 µm (mean ± SD) in the bucillamine-treated rats, which was significantly decreased compared to that in controls (60.8 ± 9.2 µm) (P < 0.01). Conclusions. Our results suggest that bucillamine may inhibit the development of laser-induced CNV in rats.

Dynamic observation of selective accumulation of a photosensitizer and its photodynamic effects in rat experimental choroidal neovascularization.

Purpose The authors investigated the selective accumulation of a photosensitizer, ATX-S10(Na), in experimental choroidal neovascularization (CNV) in rats using a highly sensitive colorchromatic charge coupled device (CCD) camera. Methods To detect the development of experimental CNV in 30 rats, the animals were followed weekly with simultaneous fluorescein and indocyanine green angiography. After injecting ATX-S10(Na), the authors detected fluorescence from the photosensitizer using a highly sensitive color CCD camera. The camera was connected to a surgical microscope, under which rat fundi were observed through a coverglass in contact with the cornea. The retinas were excited with 405–435 nm light, and the light emitted from the photosensitizer passed through a 680-nm bandpass filter before being detected by the CCD camera. Results Immediately after injection, fluorescence appeared in the retinal vessels and then the entire retina. Thirty minutes postinjection, the intensity of the fluorescence was still strong from the whole retina, and the CNV was not detected. One hour after injection, retinal fluorescence was weak but still observable; 1.5 hours postinjection, retinal fluorescence was undetectable but fluorescence was strong from the CNV. Under the optimum therapeutic conditions, CNV was effectively occluded. Conclusion ATX-S10(Na) selectively accumulates in the CNV in rats. The optimum therapeutic timing is approximately 1.5 hours postinjection of the dye in this CNV model.

Inhibitory effects of bucillamine on increased blood-retinal barrier permeability in streptozotocin-induced diabetic rats

Purpose. To investigate the effect of bucillamine for prevention of increasing blood-retinal barrier (BRB) permeability in streptozotocin (STZ)-induced diabetic rats. Methods. The groups included control and STZ-induced diabetic rats treated with or without bucillamine. Six months after intervention, the concentrations of reduced and oxidative glutathione (GSH and GSSG) in the retina were measured biochemically. In addition, vitreous fluorescein, which leaks from the vessels after intravenous injection of fluorescein sodium, was measured to evaluate BRB permeability. To evaluate the scavenging ability against the reactive oxygen species (ROS) in vitro, the second-order rate constant for the reaction of bucillamine with ROS was estimated from the kinetics based on the rate constant for the reaction of ROS. Results. The BRB permeability was significantly higher (p = 0.01) in diabetic rats not treated with bucillamine, and bucillamine inhibited the BRB permeability. The GSH concentration and the GSH/GSSG ratio in the retinas decreased in diabetic rats not treated with bucillamine; bucillamine inhibited the decrease of the GSH concentrations. The ROS scavenging activity of bucillamine was similar with that of GSH. Conclusions. In diabetic retinas, oxidative stress might increase, which may be one of the causes of BRB breakdown. The antioxidant effects of bucillamine might take part in inhibition of increased permeability of the BRB in diabetes.