Biomedical subjects

Hideaki Hara

Publications and source records attributed to Hideaki Hara.

42 records · Page 3Linked to original sources

PubMed2003

New fluoroprostaglandin F(2alpha) derivatives with prostanoid FP-receptor agonistic activity as potent ocular-hypotensive agents.

To find new prostanoid FP-receptor agonists possessing potent ocular-hypotensive effects with minimal side effects, we evaluated the agonistic activities of newly synthesized prostaglandin F(2alpha) derivatives for the prostanoid FP-receptor both in vitro and in vivo. The iris constrictions induced by the derivatives and their effects on melanin content were examined using cat isolated iris sphincters and cultured B16 melanoma cells, respectively. The effects of derivative ester forms on miosis and intraocular pressure (IOP) were evaluated in cats and cynomolgus monkeys, respectively. Of these derivatives, 6 out of 12 compounds were more potent iris constrictors, with EC(50) values of 0.6 to 9.4 nM, than a carboxylic acid of latanoprost (EC(50)=13.6 nM). A carboxylic acid of latanoprost (100 microM) significantly increased the melanin content of cultured B16 melanoma cells, but some 15,15-difluoro derivatives, such as AFP-157 and AFP-172, did not. Topically applied AFP-168, AFP-169 and AFP-175 (isopropyl ester, methyl ester and ethyl ester forms, respectively, of AFP-172) induced miosis in cats more potently than latanoprost. AFP-168 (0.0005%) reduced IOP to the same extent as 0.005% latanoprost (for at least 8 h). These findings indicate that 15,15-difluoroprostaglandin F(2alpha) derivatives, especially AFP-168, have more potent prostanoid FP-receptor agonistic activities than latanoprost. Hence, AFP-168 may be worthy of further evaluation as an ocular-hypotensive agent.

Administration, Topical↗

PubMed2003

[Effects of ocular hypotensive agents on the circadian rhythm in intraocular pressure in rabbits as measured by telemetry].

PURPOSE: To establish a telemetry system for measuring intraocular pressure (IOP) in rabbits and to evaluate the effects of topical application of ocular hypotensive agents on the circadian rhythm of IOP. SUBJECTS AND METHODS: We developed a telemetry system in rabbits housed under a 12-hour light-dark cycle (light and dark phases: 7:00-19:00, 19:00-7:00, respectively). The IOP resulting from a single topical application of ocular hypotensive agents was measured by telemetry during the light phase and the dark phase. RESULTS: The values measured by the telemetry were positively correlated to the value of the anterior chamber pressure measured by a transducer in range from 5 to 50 mmHg (r = 0.987). A single topical application of timolol maleate (0.5%), dorzolamide hydrochloride (1%), and dipivefrine hydrochloride (0.1%) caused no significant reduction in IOP in the light phase, but they did in the dark phase. A single topical application of bunazosin hydrochloride (0.01% or 0.1%) had significant ocular hypotensive effects in both phases. CONCLUSION: These findings indicate that the different effects of ocular hypotensive agents on circadian rhythms of IOP can be measured by the telemetry. Telemetry may be useful for evaluation of ocular hypotensive agents and the circadian rhythm of IOP.

Animals↗

PubMed2002

Protective effects of timolol against the neuronal damage induced by glutamate and ischemia in the rat retina.

The purpose of this study was to determine whether timolol, an ocular hypotensive drug, has retinal neuroprotective effects in experimental in vitro and in vivo models. For in vitro studies, we used retinal neuron cultures from rat embryos and purified retinal ganglion cells (RGCs) from newborn rats. In the former, neurotoxicity was induced using 1 mM glutamate and cell viability was assessed. In RGCs, neurotoxicity was induced using 25 microM glutamate for 3 days and cell viability was assessed. For the in vivo study, we used a rat model of retinal ischemic injury induced by elevating intraocular pressure (IOP) by raising the hydrostatic pressure. The retinal damage was evaluated by counting the number of cells in the ganglion cell layer (GCL) and by examining the a- and b-waves in the electroretinogram (ERG). For the intraocular distribution study, 0.5% [3H]timolol was topically applied to rat eyes, and these were enucleated after various intervals and divided into parts. Each part was combusted and the radioactivity measured. Timolol (0.1 and 1 microM) markedly reduced the glutamate-induced neuronal cells in retinal neuron cultures and in RGCs. After ischemic-reperfusion, both the number of cells in the GCL and a- and b-waves in the ERG decreased; however, topically applied 0.5% timolol reduced these effects. Topically applied 0.5% timolol was detected at a concentration of approximately 1 microg/g wet tissue in retina-choroid at 30 min after its application. In conclusion, timolol was effective against retinal neuron damage both in vitro and in vivo. Furthermore, topically applied timolol reached the retina-choroid. These findings suggest that timolol has a direct neuroprotective effect against retinal damage.

Action Potentials↗

PubMed2002

Brain-derived neurotrophic factor inhibits changes in soma-size of retinal ganglion cells following optic nerve axotomy in rats.

To determine if optic nerve axotomy affects the cell soma size of retinal ganglion cells and to establish whether such quantitative analysis is useful as a new way of evaluating retinal ganglion cell damage, we measured the changes in both the number and soma size of retinal ganglion cells after optic nerve axotomy in rats. Retinal ganglion cells were retrogradely labeled by fluoro-gold injection into the superior colliculus, and the soma size was measured using image-analysis software. We detected a decrease in the proportion of large-sized retinal ganglion cells that was significant at 3, 5 and 7 days after the axotomy, and an increased proportion of small-sized ones that was significant at 5 and 7 days after the axotomy, indicating that retinal ganglion cells shrank following axotomy, that there was a shift away from the largest category of retinal ganglion cells towards the smallest category. On days 3 and 5 post-axotomy, there was no significant change in the proportion of medium-sized retinal ganglion cells. Intravitreal injection of brain-derived neurotrophic factor one hour before the axotomy significant inhibited the increase in the proportion of small-sized retinal ganglion cells otherwise seen at 3 days after the axotomy. These results may suggest that larger retinal ganglion cells are more sensitive to optic nerve axotomy than small- and medium-sized ones, and that a quantitative analysis of soma size is a useful way of detecting retinal ganglion cell damage in the early phase after axotomy.

Animals↗

PubMedDate not supplied

Effects of topically instilled bunazosin hydrochloride and other ocular hypotensive drugs on endothelin-1-induced constriction in rabbit retinal arteries.

PURPOSE: To compare the inhibitory effect of topically instilled bunazosin hydrochloride (bunazosin), a selective alpha(1)-adrenoceptor antagonist, on the endothelin (ET)-1-induced vasoconstriction in rabbit retinal arteries with the effects of other ocular hypotensive drugs. METHODS: ET-1 was injected into the central part of the vitreous of both eyes of pigmented rabbits. Color fundus photographs were taken 5 min before and 60 min after the injection. The average diameters of the two major retinal arteries at the rim of the optic nerve head (ONH) were normalized with respect to ONH diameter. Fifty microliters of 0.01% bunazosin, or 0.12% isopropyl unoprostone (unoprostone), 1% dorzolamide hydrochloride (dorzolamide), 0.25% nipradilol, 0.5% betaxolol hydrochloride (betaxolol), or 0.5% timolol maleate (timolol) was instilled into one eye of each rabbit 60 min before the ET-1 injection. The series of experiments was performed as masked tests. RESULTS: Bunazosin and unoprostone inhibited the ET-1-induced constriction of retinal arteries by 103% (P = 0.012 versus contralateral eyes) and 50% (P = 0.037), respectively. Dorzolamide, nipradilol, betaxolol, and timolol had no significant effects in this experiment. CONCLUSIONS: Under our experimental conditions, bunazosin and unoprostone inhibited the ET-1-induced constriction. Hence, bunazosin and unoprostone may be clinically more effective against ET-1-related retinal diseases.

Administration, Topical↗

PubMedDate not supplied

Vitreous fluid levels of beta-amyloid((1-42)) and tau in patients with retinal diseases.

PURPOSE: A decrease in beta-amyloid(1-42) (Abeta42) and an increase in tau in the cerebrospinal fluid are reported to be characteristic phenomena in Alzheimer's disease patients. To test the idea that Abeta42 and tau contribute to the development of retinal diseases, we measured Abeta42 and tau concentrations in the vitreous fluid from patients with macular hole (n = 13), diabetic retinopathy (n = 15), or glaucoma concurrent with other ocular diseases (n = 8). METHODS: Vitreous samples were collected from patients who underwent vitrectomy, and sensitive and specific enzyme-linked immunosorbent assays were used to determine the concentrations of Abeta42 and tau. RESULTS: By comparison with the levels in the control macular-hole patients (33.9 +/- 7.1 pg/ml for Abeta42; 3.3 +/- 3.2 pg/ml for tau), there was a significant decrease in the Abeta42 level and a significant increase in the tau level in patients with diabetic retinopathy (1.8 +/- 1.9 pg/ml for Abeta42, P = 0.002; 153.7 +/- 71.6 pg/ml for tau, P = 0.041) or glaucoma concurrent with other ocular diseases (2.8 +/- 1.8 pg/ml for Abeta42, P = 0.006; 113.6 +/- 43.1 pg/ml for tau, P = 0.023). CONCLUSIONS: Our findings indicate the possibility of a role for Abeta42 and tau in the pathogenesis of some retinal diseases.

Aged↗