Masaaki Ohashi

The efficacy of TonoLab in detecting physiological and pharmacological changes of mouse intraocular pressure--comparison with TonoPen and microneedle manometery.

Purpose: The efficacy of two non-invasive tonometers, TonoLab and TonoPen XL, in detecting physiological or pharmacological changes of intraocular pressure (IOP) in mouse eyes, was assessed by comparison with a microneedle method. Material and Methods: C57BL6 mice, bred under the 12-hr light and dark cycle over 2 weeks, were used. Under systemic anesthesia, mouse eyes were cannulated by a microneedle connected to a transducer and a water reservoir. We manipulated the intracameral pressure by changing the reservoir height, and obtained tonometer readings at each pressure (n = 39) with TonoLab and TonoPen XL. The correlation between each tonometer and the manometer was analyzed. Then the diurnal variation of IOP in the light and dark phases, and the IOP-lowering effect at 2 hr after latanoprost instillation, were measured with TonoLab, TonoPen XL, and a microneedle tonometer (n = 8). Results: In mouse eyes, TonoPen XL could not show reliable scores, but TonoLab readings showed a strong correlation with manometer readings (y = 0.87x – 0.27, r2 = 0.917). Nocturnal elevation of IOP in mouse eyes was significantly indicated with TonoLab and a microneedle tonometer (p < 0.001), but not with TonoPen XL. Latanoprost significantly reduced IOP by 2.1 ± 2.8 and 2.0 ± 1.0 mmHg with TonoLab and a microneedle tonometer, but not with TonoPen XL. Conclusion: TonoLab provides similar readings to a microneedle tonometer, and diurnal variation and drug effect were detectable in mouse eyes. TonoLab promises to be a non-invasive and useful method to evaluate physiological and pharmacological studies in mouse eyes.

Efficacy of TonoLab in detecting physiological and pharmacological changes in rat intraocular pressure: Comparison of TonoPen and microneedle manometry

PurposeTo assess the efficacy of two noninvasive tonometers, TonoLab and TonoPen-XL, in detecting physiological or pharmacological changes of intraocular pressure (IOP) in rat eyes, by comparing them with the microneedle method.MethodsSprague Dawley rats, bred under a 12-h light-and-dark cycle, were used. Under systemic anesthesia, eyes were cannulated by a microneedle connected to a transducer and a water reservoir. Variable intracameral pressure was attained by changing the reservoir height, and the resulting tonometer readings were compared. Then, the daytime and nighttime IOP, and the effect at 2 h after latanoprost instillation, were measured with the three devices.ResultsTonoLab and TonoPen-XL readings (y) were strongly correlated with microneedle tonometer readings (x) (y = 0.96x − 4.3, r2 = 0.985, and y = 0.48x + 3.9, r2 = 0.985, respectively), but TonoPen-XL readings were only half those of the microneedle tonometer. Nocturnal elevation of IOP was significant both with TonoLab and with the microneedle tonometer (P < 0.001), but not with TonoPen-XL. Latanoprost significantly elevated IOP by 3.0 ± 2.1 with TonoLab and by 1.1 ± 1.1 mmHg with the microneedle tonometer (P < 0.05), but not with TonoPen-XL.ConclusionTonoLab provides readings similar to those of a microneedle tonometer, and diurnal variations and drug effects were detectable. TonoLab promises to be a noninvasive and useful method for physiological and pharmacological studies in rat eyes.

Effects of Topical Travoprost and Unoprostone on Optic Nerve Head Circulation in Normal Rabbits

Purpose: To evaluate the effect, and the duration of the effect, of topically administrated travoprost and unoprostone on optic nerve head (ONH) circulation in Dutch rabbits. Methods: First, travoprost (0.004% solution) or unoprostone (0.12% solution) was unilaterally instilled once, or once daily (travoprost) or twice daily (unoprostone) for 7 days in Dutch rabbits. The ONH tissue blood velocity (NBONH) was measured using the laser speckle method at 30 and 60 min after a single instillation of travoprost or unoprostone, and before and at 1, 6, and 12 hr (travoprost or unoprostone) and 24 hr (travoprost only) after the last instillation of the aforementioned 7-day instillation regimen. Second, similar experiments were conducted with indomethacin (5 mg/kg) pretreatment. Results: Both travoprost and unoprostone significantly increased NBONH only in the treated eyes after a single instillation (p = 0.011 to 0.038); this effect was abolished by indomethacin pretreatment. In the 7-day instillation regimen, NBONH was increased by 11%, 40%, 17%, 16%, and 12% only in the treated eyes just before and at 1, 6, 12, and 24 hr after the final instillation of travoprost, respectively, and increased by 10%, 25%, 13%, and 14% only in the treated eyes just before and at 1, 6, 12 hr after the final instillation of the unoprostone, respectively. Conclusions: Topical travoprost or unoprostone significantly increased the ONH blood velocity with a single instillation and the effect persisted for 24 hr after a 7-day instillation. The effects of these drugs against retinal and ONH circulation are probably associated with the production of endogenous prostaglandins.

Neuroprotective Effect of the Novel Na+/Ca2+ Channel Blocker NS-7 on Rat Retinal Ganglion Cells

PurposeTo investigate whether NS-7, 4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride, a novel Na+/Ca2+ channel blocker, can protect the rat retina subjected to ischemia–reperfusion insult.MethodsTo evaluate the protective effect of NS-7 against retinal damage, the drug was administered before and after ischemia–reperfusion. Damage to the retina was assessed by measuring the thickness of the inner plexiform layer (IPL) and the outer nuclear layer (ONL) of each eye. In a subsequent experiment, electroretinographic (ERG) evaluation was also used.ResultsIn histopathologic evaluation, ischemia–reperfusion injury caused a significant reduction of IPL thickness (measured as the IPL/ONL ratio). In the NS-7-treated group, retinal damage was partially prevented by a concentration of 0.25 mg/kg per day. In the ERG evaluation, ischemia–reperfusion injury caused a reduction of A- and B-wave amplitudes. NS-7 treatment significantly prevented the reduction of the B wave at a concentration of 0.1 or 0.3 mg/kg, while the reduction of the A wave was not significantly affected.ConclusionsNS-7 has neuroprotective effects against retinal damage resulting from subjection to ischemia. In addition, NS-7 can be used as an agent for treating acute ischemic retinopathy, including diseases associated with very high intraocular pressure, such as acute angle-closure glaucoma. Jpn J Ophthalmol 2005;49:371–376

Local effect of topical FP-receptor agonists on retinal vessels of the ipsilateral posterior retina in normal rabbit eyes

Purpose:  To determine whether a topically instilled prostaglandin analogue inhibits endothelin‐1 (ET‐1)‐induced vasoconstrictive effects in the posterior retina by its local effects, and the duration of the effect in normal rabbit eyes.

Bilateral Iris Metastases from Prostate Cancer

BACKGROUND Iris metastases of malignant tumors are not common, and most of the cases are unilateral. To our knowledge, there has been no report of bilateral iris tumors metastasized from prostate cancer. CASE A 71-year-old man with a history of prostate cancer presented with bilateral iris tumors and secondary glaucoma. He had had multiple bone metastases, and had undergone chemotherapy. OBSERVATIONS Gray-white fleshy tumors spread in the iris of both eyes. Iridocyclitis and secondary glaucoma were present. After external beam radiotherapy, the iris tumors regressed remarkably in volume. CONCLUSIONS We observed a rare case of bilateral iris tumors, which had probably metastasized from prostate cancer. The tumors were well controlled with conservative therapies including radiation. We believe this article is the first report of bilateral iris tumors metastasized from prostate cancer.

Ocular Distribution After Topical Instillation and Potential Neuroprotective Effect After Intravitreal Injection of the Calcium Channel Blocker Iganipidine

Purpose: To investigate the effects of iganidipine, a new calcium antagonist on glutamate agonist–induced retinal damage. Methods: Iganidipine was injected with N-methyl-d-aspartate (NMDA) or kainic acid (KA) into the rat vitreous, and the retina was histologically examined. After co-injection with KA, the number of DiI-labeled retinal ganglion cells was also counted. Rabbits received unilateral instillation of 0.03% iganidipine twice daily for 14 days, and the iganidipine level in the posterior retina-choroid was determined by liquid chromatography/mass spectrometry. Results: Coadministration of iganidipine had no significant effect on NMDA-induced thinning of the inner plexiform layer but partly suppressed KA-induced thinning at final intravitreous concentrations of 10− 8 M or higher, which was confirmed by counting the ganglion cell number. The iganidipine level in the posterior retina-choroid was approximately 6.2 × 10− 7 M in the instilled eye, which was higher than on the contralateral side by 5.2 × 10− 7 M (p = 0.035). Conclusions: Iganidipine suppressed KA-induced retinal damage in rats. This suppression was achieved with a lower concentration than that resulting from unilateral instillations of iganidipine in the ipsilateral posterior retina-choroid in rabbits.