Retinal toxicity of antibiotics: evaluation by electroretinogram.

Toxicity of an intravitreal injection of gentamicin sulfate, disodium sulbenicillin and cefazolin sodium on the retina was investigated by electroretinogram in albino and pigmented rabbits. Recordings were made before injection and 2 hours and 3, 7, 14, and 21 days after injection. Significant differences were found in the susceptibility of the electroretinogram components to various antibiotics as follows. Gentamicin 0.24 mg/0.1 ml irreversibly abolished all the components examined. Sulbenicillin 4.0, 8.0, or 12 mg/0.1 ml transiently suppressed the b-wave and the oscillatory potentials incrementally with increasing dose. Cefazolin 0.5, 2.0, or 5.0 mg/0.1 ml selectively reduced the oscillatory potentials, leaving the a- and b-waves almost unattenuated. The cefazolin-suppressed oscillatory potentials recovered within 14 days after injection. Judging from the most susceptible electroretinogram components to each antibiotic, we recommend intravitreal doses of these antibiotics for clinical use as follows: gentamicin 0.1 mg/0.1 ml, sulbenicillin 2 mg/0.1 ml, and cefazolin 0.25 mg/0.1 ml.

Microelectrode depth study of the electroretinographic oscillatory potentials in the frog retina.

The depth profile of the electroretinographic oscillatory potentials was studied in the isolated frog retina. The intraretinal electrode was introduced from the receptor side, and the reference electrode was placed on the vitreal side. The electroretinogram, recorded either transretinally or with the electrode tip in the receptor layer, showed 4 to 10 oscillatory potential wavelets. As the electrode was advanced proximally, the wavelets disappeared as a function of retinal depth. The wavelets with longer peak latencies disappeared earlier, and only the first one or two wavelets could be identified when the electrode was in the inner plexiform layer. These findings indicate that the oscillatory potentials are generated between the inner and outer plexiform layers and that the earlier wavelets originate in the more proximal retina. The results are consistent with the notion that the oscillatory potentials are generated by synaptic feedback circuits.

Spectroscopic studies of brunescent cataractous lenses.

The absorption spectra of brunescent cataractous lenses and their homogenates were analyzed under various conditions by using a double wavelength spectrophotometer. The absorption spectra of the samples were in good agreement with those of synthetic xanthommatin derived from 3-hydroxykynurenine. The results provided evidence that brown pigment in the brunescent cataractous lenses is mainly composed of xanthommatin.

Electrophysiological study of the pigmentfarbenamblyopie.

The spectral sensitivity of the rapid off-response in the electroretinogram is found to be abnormal in some cases of Pigmentfarbenamblyopie or congenital red-green color deficiency. We hypothesize that there exists a fragile cone mechanism in these cases which show an abnormality in spectral sensitivity of the rapid off-response.

Effects of antibiotics on the in vitro ERG of the albino rabbit. Penicillins and cephalosporins antibiotics.

This study describes the effects of penicillin G (PC-G) potassium, PC-G sodium, cloxacillin sodium (MCIPC), disodium sulbenicillin (SBPC), cefazolin sodium (CEZ) and cefsulodin sodium (CFS) on the in-vitro electroretinogram (ERG) of the albino rabbit. The b-wave and oscillatory potentials (OPs) were unchanged by 0.1 mM PC-G potassium or PC-G sodium. The OPs were slightly suppressed by 0.3 mM of either drug. While the a- and b-waves were not deteriorated, the OPs were greatly suppressed by 1.0 mM concentration. The effect of PC-G on the ERG was characterized by a selective suppression of the OPs. The b-wave and OPs were not suppressed by 0.03 mM MCIPC. They were slightly suppressed by 0.05 mM MCIPC. The a-wave, b-wave and OPs were not deteriorated by 1.0 mM SBPC. The b-wave and OPs were suppressed by 3.0 mM or 6.0 mM SBPC respectively. These changes appeared to be dose-dependent. Since the b-wave and OPs were concomitantly suppressed by both MCIPC and SBPC, these antibiotics, unlike PC-G, did not selectively suppress the OPs. The b-wave and OPs were unchanged by 0.1 mM CEZ or CFS. The OPs were slightly suppressed by 0.3 mM CEZ or CFS. CEZ or CFS of 1.0 mM did not deteriorate the a- and b-waves, but selectively suppressed the OPs. The effects of CEZ and CFS on the ERG were characterized by a selective suppression of the OPs. The above-described changes in the ERG were reversible.

Acetazolamide-induced changes of the membrane potentials of the retinal pigment epithelial cell.

Acetazolamide-induced changes of the apical (Vap) and basal (Vba) membrane potentials of the retinal pigment epithelial cell were studied in an in-vitro retinal pigment epithelium (RPE)-choroid of the frog. Both Vap and Vba were hyperpolarized by acetazolamide placed on either the apical or basal side of the RPE. In all cases, acetazolamide on the apical side hyperpolarized Vba more than Vap and decreased the transepithelial potential (TEP) across the RPE. In most cases, acetazolamide on the basal side hyperpolarized both Vap and Vba to almost equal degrees and hardly changed the TEP. We conclude that the Diamox response (a decrease of the ocular standing potential induced by an intravenous sodium acetazolamide) may be triggered by effects of acetazolamide on the apical side of the RPE and generated mainly by a hyperpolarization of the basal membrane of the RPE cell.

Suppression of the hyperosmolarity response after cataract surgery.

The hyperosmolarity response was recorded with the electrooculogram in the dark before and after cataract extraction, to investigate a possible disorder in the retinal pigment epithelium after cataract extraction. The hyperosmolarity response was suppressed one week after surgery, especially after intracapsular extraction. The response recovered up to the preoperative level in most cases one or two months after surgery. These findings indicate reversible functional disorders of the pigment epithelium after cataract extraction, particularly intracapsular. This dysfunction can be revealed by the hyperosmolarity response. This response is clinically useful for diagnosis of pigment epitheliopathy after cataract extraction.

Quantitative analysis of the suppressive effect on the light rise of the hypertonic solution.

We previously reported the hyperosmolarity response (a decrease of the ocular standing potential by hyperosmolarity) as a new clinical test of the retinal pigment epithelium (RPE) activity. In the present study a hypertonic solution (Fructmanit, 1.4 X 10(3) m0sm/1) was intravenously injected for 20 min in proportion to a subject's total blood volume (TBV). At the injection speed of 5, 10, and 15% of the subjects' TBV per hour the mean amplitude of the hyperosmolarity response in normal subjects was 19.7, 30.1 and 36.4% respectively. The amplitude of the hyperosmolarity response depends on the logarithm of the dose of the hypertonic solution within the range of the dose tested. We previously found that hyperosmolarity suppresses the light rise. The present study investigated this suppressive effect in a quantitative manner. The light rise (a full-field illumination of 1.2 X 10(3) cdl/m2) was dose-dependently suppressed by Fructmanit. The mean of the light rise to dark trough ratio in normal subjects was 1.81 with no osmotic stress, and 1.64, 1.41 and 1.29 respectively at the injection speeds of 5, 10, and 15%. The suppression of the light rise by hyperosmolarity is compatible with the view that the hyperosmolarity response and the light rise share the basal membrane of the RPE as the main site of their generation.

Spectral characteristics of early receptor potential in congenital red-green color blindness.

The spectral response curve (amplitude versus wavelength) of the R2 of the early receptor potential (ERP) was studied in normal, protan, and deutan subjects. The R2 amplitude peaked at 520 nm in most normal subjects. The R2 at long wavelengths was smaller than normal in protans and larger than normal in deutans when the maximum amplitudes were normalized to 100% at the peak. The ratio of the R2 amplitude at 460 nm to that at 600 nm clearly differed between protans and deutans. The ERP and the rapid off-response, which is mainly due to the cessation of the late receptor potential, were recorded in the same subjects. The ratio of the sensitivity of the rapid off-response at 500 nm to that at 600 nm was correlated with the ratio of the R2 amplitude at 460 nm to that at 600 nm (correlation coefficient, 0.823, p less than 0.001). This study, in conjunction with our previous study, indicates that the abnormality is in the outer segments of the cones in protans and deutans.

Electroretinographic off-response in congenital red-green color deficiency and its genetic carrier.

The spectral sensitivity of the rapid off-response in the electroretinogram is found to be abnormal in all protans and deutans so far tested, and in some of their genetic carriers. The rapid off-response is an objective means of assessing the x-linked recessive color deficiencies and their carrier state.

Microelectrode depth study of electroretinographic b- and d-waves in frog retina.

The depth profiles of the b- and d-waves of the electroretinogram were studied in the isolated frog retina placed with its receptor side up. The electrode was introduced into the retina from the receptor side and the reference electrode was placed on the vitreal side. The b-wave was maximum in amplitude in the receptor layer, and decreased as the electrode was advanced proximally from the outer plexiform layer until it disappeared at the inner limiting membrane. The b-wave in the inner plexiform layer was different from that in the distal portion of the inner nuclear layer in form and peak latency. The results suggested that the b-wave is generated in the layers between the inner limiting membrane and the outer plexiform layer, and that at least two processes are involved in the generation of the b-wave. The depth profile of the d-wave resembled that of the b-wave except in the receptor layer; it was recorded in the whole retinal layers as was the b-wave, and decreased as the electrode was advanced proximally until it disappeared at the inner limiting membrane. The peak latency of the d-wave was longer in the inner plexiform layer than in the distal portion of the inner nuclear layer. The results indicated that the d-wave consists of the off-response of the late receptor potential and the postsynaptic components, the latter being generated by a similar mechanism as the b-wave.