Kano Hiroi

Specific deficit of the ON response in visual transmission by targeted disruption of the mGIuR6 gene

Taking advantage of the restricted expression of metabotropic glutamate receptor subtype 6 (mGluR6) in retinal ON bipolar cells, we generated knockout mice lacking mGluR6 expression. The homozygous mutant mice showed a loss of ON responses but unchanged OFF responses to light. The mutant mice displayed no obvious changes in retinal cell organization nor in the projection of optic fibers to the brain. Furthermore, the mGluR6-deficient mice showed visual behavioral responses to light stimulation as examined by shuttle box avoidance behavior experiments using light exposure as a conditioned stimulus. The results demonstrate that mGluR6 is essential in synaptic transmission to the ON bipolar cell and that the OFF response provides an important means for transmitting visual information.

Role of Nitric Oxide during the Initial Phase of Reperfusion after Retinal Ischemia in the Rat

The onset of reperfusion and the recovery of the ERG b-wave following retinal ischemia was examined among three groups of rats: group 1 (n = 12) and group 2 (n = 6) received pretreatment with NG-nitro-L-arginine (20 mg/kg, i.p., 2 h before ischemia) followed by intravenous injection of saline (group 1) or of 200 mg/kg L-arginine (group 2) 5 min before the end of ischemia; group 3 (n = 7) received saline pretreatment followed by intravenous injection of saline as a control. Group 1 showed delayed onset of reperfusion compared to the other two groups and a reduction in the rate of the b-wave recovery compared to the control on the 1st day after reperfusion (group 1 vs. group 3; p = 0.0357). The L-arginine posttreatment significantly increased the b-wave recovery (group 2 vs. group 1; p = 0.0005 on day 1 and p < 0.0006 on day 3). The rate of the b-wave recovery in group 1 was inversely proportional to the time to establish complete reperfusion. Inhibition of nitric oxide synthase during the initial phase of reperfusion may worsen the recovery of the b-wave following retinal ischemia, at least in part, by inhibiting establishment of reperfusion.

Effects of Intravenous Superoxide Dismutase and Catalase on Electroretinogram in the Cat Postischemic Retina

We examined the effects of the antioxidant enzymes, 10,000 U/kg of superoxide dismutase (SOD) and 50,000 U/kg of catalase (CAT) on cat electroretinograms during the reperfusion after retinal ischemia. The intravenous administrations of SOD and CAT promoted the recovery of the c-wave after 30 min of ischemia but not the b-wave. At 5 min after onset of reperfusion, SOD- and CAT-treated eyes showed 90 and 110% recovery of the c-wave amplitude respectively, against 50% recovery in the untreated eyes. These results suggested that the oxygen-derived free radicals affected the retinal pigment epithelium at the early period of reperfusion.

Intraretinal analysis of electroretinogram with K+ microelectrodes during acute intraocular pressure elevation

We examined the effects of acute intraocular pressure elevation on the intraretinal electroretinogram in the cat dark-adapted eye. Perfusion pressure of the eye (mean arterial pressure minus intraocular pressure) was regulated within the range of 25–75 mm Hg by increasing the intraocular pressure, which was adjusted by changing the height of the reservoir of balanced salt solution perfused into the eye through a needle placed in the anterior chamber. The vitreal electroretinogram, transepithelial c-wave, slow PIII and light-evoked decrease in extracellular K+ concentration were recorded during intraocular pressure elevation in the darkadapted retina. The c-wave increased in amplitude between 40 and 75 mm Hg of perfusion pressure and decreased below 40 mm Hg in some cases. These changes were unrelated to the standing potential. The transepithelial c-wave, slow PIII and light-evoked decrease in extracellular K+ concentration were larger in the range of perfusion pressure examined. These suggest that some factor induces electroretinographic changes that are not readily explained by hypoxia or pH changes alone.

Design of a new disposable ERG electrode.

A new electrode for electroretinography (ERG) has been produced. The new device made of gold filament was applied as corneal and noncorneal electrod. Flash ERG and pattern ERG were recorded in normal subjects using this new electrode and compared with those made by available electrodes. There were so significant differences in amplitude and latency between the new electrode placed on the cornea and the JET-type electrode. For pattern ERG there were no significant differences between the new electrode placed in the lower fornix and a gold-foil-type electrode. As this new electrode is less expensive and more comfortable than the available electrodes, it is clinically useful.

Effects of Ischemia-Reperfusion on Light-Evoked Alkalinization Outside Rod Photoreceptors in the Cat Retina

The effects of ischemia-reperfusion on the light-evoked alkalinization, which reflects the metabolism of rod photoreceptors, were studied in the dark-adapted cat retina in vivo. We recorded the pH value in the extracellular space surrounding rod photoreceptors with double-barreled H(+)-selective microelectrodes. The light-evoked alkalinizations at the outer nuclear layer were diminished during reperfusion after 10-30 min of ischemia which was induced by an increase of the intraocular pressure above the arterial systolic pressure. This result suggests that the rod metabolism might be suppressed during reperfusion after ischemia.