Amacrine cells coupled to ganglion cells via gap junctions are highly vulnerable in glaucomatous mouse retinas

We determined whether the structural and functional integrity of amacrine cells (ACs), the largest cohort of neurons in the mammalian retina, are affected in glaucoma. Intraocular injection of microbeads was made in mouse eyes to elevate intraocular pressure as a model of experimental glaucoma. Specific immunocytochemical markers were used to identify AC and displaced (d)ACs subpopulations in both the inner nuclear and ganglion cell layers, respectively, and to distinguish them from retinal ganglion cells (RGCs). Calretinin- and γ-aminobutyric acid (GABA)-immunoreactive (IR) cells were highly vulnerable to glaucomatous damage, whereas choline acetyltransferase (ChAT)-positive and glycinergic AC subtypes were unaffected. The AC loss began 4 weeks after initial microbead injection, corresponding to the time course of RGC loss. Recordings of electroretinogram (ERG) oscillatory potentials and scotopic threshold responses, which reflect AC and RGC activity, were significantly attenuated in glaucomatous eyes following a time course that matched that of the AC and RGC loss. Moreover, we found that it was the ACs coupled to RGCs via gap junctions that were lost in glaucoma, whereas uncoupled ACs were largely unaffected. Our results suggest that AC loss in glaucoma occurs secondary to RGC death through the gap junction–mediated bystander effect. J. Comp. Neurol. 527:159–173, 2019. © 2016 Wiley Periodicals, Inc.     

Safety of intravitreal triamcinolone acetonide:an electrophysiologic and histopathological study in rabbits

AIM

To evaluate the retinal safety of various doses of intravitreal triamcinolone acetonide (TA) in rabbits.

Methods

Thirty New Zealand albino rabbits were divided into five groups (six animals each). In group 1 (control group), each animal received a single intravitreal injection of 0.1mL phosphate buffered saline. In groups 2, 3, 4 and 5, each rabbit received a single intravitreal injection of 4, 8, 16 and 32mg of TA, respectively. Each dose was contained in 0.1mL phosphate buffered saline. Clinical ocular examinations were performed before the injection and on the 1st, 3rd, 10th and 17th post-injection days. A standard dark adapted electroretinogram (ERG) was obtained before injection and on the 3rd, 10th and 17th post-injection days. After 17d, animals were sacrificed and their eyes prepared for pathological examination.

RESULTS

By monitoring ERG as a functional index for the retina, intravitreal injection of 4mg TA showed no significant ERG changes. At doses of 8, 16 and 32, hyper-abnormal responses in a- and b- waves of ERG were detected on the 3rd post-injection day. These changes gradually returned back to normal limits after 17d. Histopathological examination of the retina of all animals showed no pathological changes.

CONCLUSION

High doses of intravitreal TA seemed to have enhancing effects on the retinal function with gradual return to normal limits with no pathological changes detected in examined eyes.     

Macular electroretinograms to flicker and pattern stimulation in lamellar macular holes

Steady-state macular (9° × 9°) electroretinograms in response to either sinusoidal flicker (focal electroretinogram) or counterphased sinusoidal gratings (pattern electroretinogram) were recorded in 14 patients with inner lamellar macular holes, in 4 patients with full-thickness macular holes and in 14 age-matched controls. Fourier analysis of focal and pattern electroretinograms yielded three main components: a first and a second harmonic to flicker, and a second harmonic to pattern. Recent evidence indicates that the first harmonic to flicker is of receptoral origin, whereas the flicker and pattern second harmonics represent, at least in part, the activity of different generators in the inner retina. When compared to controls, patients with inner lamellar holes showed significant amplitude reduction and phase delay for both flicker and pattern second harmonics, but not for the flicker first harmonic. Patients with full-thickness holes showed significant amplitude reduction also for the flicker first harmonic. These results indicate a prevalent functional involvement of the inner retina in lamellar macular holes, which can be clinically detected by evaluating focal and pattern electroretinogram second harmonics.Abbreviations ILH inner lamellar hole - OLH outer lamellar hole     

Relationships between the electroretinogram a-wave,b-wave and oscillatory potentials and their application to clinical diagnosis

The electroretinogram is the electrical response of the retina to a light stimulus. The amplitude and temporal pattern of its components, the a-wave, the b-wave and the oscillatory potentials, depend on the functional integrity of the retina, on the intensity of test flash reaching the retina and on the ambient illumination. The latter contributions to the normal variability in the electroretinogram can be circumvented by constructing the relationships between the different electroretinogram waves. The electroretinogram responses were recorded from 18 dark-adapted subjects with normal vision. The slope of the a-wave and the amplitude of the b-waves were measured in the time domain. The oscillatory potentials were isolated by a digital filter and were transformed to the frequency domain for quantitative measurement. The relationship between each pair of variables could be fitted by linear segments. Our findings suggest that this mode of electroretinogram analysis can be useful in localizing the site of action of retinal disorders and that the relationship between the a-wave slope and the power density of the oscillatory potentials is a useful index for identifying disorders of the inner retina.     

Electrophysiologic findings in optic nerve dysfunction associated with multiple evanescent white-dot syndrome

Electrophysiologic findings in a case of multiple evanescent white-dot syndrome were studied. A 37-year-old woman presented with multiple white dots, granularity of the macula, and optic disc swelling in her left fundus. The electroretinogram and electro-oculogram revealed abnormal findings indicative of changes in the retinal pigment epithelium and photoreceptors. In addition, relative afferent pupillary defect, enlargement of the blind spot, a decrease in the critical fusion frequency, staining of the optic disc on fluorescein angiography and prolonged latency of the P100 component with decreased amplitude in pattern-reversal visual evoked cortical potential strongly suggested dysfunction of the optic nerve in this patient.Abbreviations MEWDS multiple evanescent white-dot syndrome     

斜视性弱视伴偏中心注视眼的多焦视网膜电图表现

目的：探究斜视性弱视伴偏中心注视眼的多焦视网膜电图(mfERG)特征性变化。

方法：收集2018-01/2020-12在我院就诊的斜视性弱视伴偏中心注视患者20例作为研究组(4例为外斜视,16例为内斜视),同时收集屈光不正性弱视患者20例作为对照组。散瞳状态下检查mfERG,记录P1波的振幅密度和潜伏期。

结果：斜视组弱视眼多焦视网膜电图P1波振幅密度与対侧眼相比第一环(P=0.001),第二环(P<0.001),第三环(P=0.001),第四环(P=0.009),第五环(P=0.026)明显降低; 与对照组相比第一环(P=0.033),第二环(P=0.002),第三环(P<0.001),第四环(P=0.014)明显降低; 斜视组弱视眼潜伏期与対侧眼相比第一环(P=0.017)、第二环(P=0.001)有明显缩短,与对照组相比第二环(P=0.007)明显缩短。

结论：斜视性弱视伴偏中心注视眼的多焦视网膜电图P1波振幅密度越靠近黄斑中心凹下降越多,且与屈光不正性弱视眼相比下降更多。     

Functional and anatomical evaluation of the effect of nepafenac in prevention of macular edema after phacoemulsification in diabetic patients

AIM: To evaluate the effect of prophylactic administration of nepafenac in prevention of macular edema occurring in diabetic patients after phacoemulsification and to investigate the correlation between optical coherence tomography (OCT) foveal thickness and multifocal electroretinogram (MF-ERG) parameters. METHODS: The study included two groups. Group 1 included 50 diabetic patients with senile cataract (50 eyes, 30 females, 20 males, aged 55±7y) received nepafenac 0.1% eye drop. Group 2 included another 50 diabetic patients with senile cataract (50 eyes, 22 female, 28 males, aged 53.8±8y) did not receive nepafenac. All patients were followed up for 3mo postoperatively. OCT and MF-ERG were done preoperative and at 1wk, 1, 2 and 3mo. RESULTS: The mean foveal thickness was statistically significantly lower in Group 1. Five eyes in Group 2 developed clinical cystoid macular oedema (CMO) (10%), and no patients in Group 1 developed central macular thickening more than 50 μm. There were insignificant differences in MF-ERG amplitudes and latencies between the two groups except in the five eyes that developed CMO, there statistically significant reduction of MF-ERG amplitude with increase in foveal thickness. CONCLUSION: Perioperative nepafenac reduces the incidence of CMO following uncomplicated phacoemulsification significantly. Nepafenac has no side effects.     

Adaptive changes of inner retina function in response to sustained pattern stimulation

We have characterized adaptive changes of inner retina function in response to sustained pattern stimulation in 32 normal subjects with an age range 23-77 years by measuring changes of the pattern electroretinogram (PERG) as a function of time. Contrast-reversal stimuli had square-wave profile in space and time, with peak spatial and temporal frequency and high contrast to maximize response amplitude. The PERG signal was sampled over 5 min with a resolution of 15 s. PERG signals were non-stationary, resulting in either progressive amplitude decline or even enhancement to a plateau, with a time course that could be well described by an exponential function with a time constant of 1-2 min. Higher initial amplitudes were generally associated with amplitude decline, and lower initial amplitudes with enhancement. The delta amplitude (plateau minus initial) was a linear function of the initial amplitude. The magnitude of delta decreased with decreasing initial amplitude and inverted its sign for initial amplitudes about 1/3 lower than the maximum initial amplitude measured, but still about 3-4 times larger than the noise. Amplitude decline was generally associated with phase lag, whereas amplitude enhancement was associated with phase advance. Altogether, PERG generators appear to slowly adjust their gain in order to keep their sustained activity at an intermediate level that is rather independent of the level of activity at stimulus onset. This behavior is reminiscent of a buffering mechanism, where glial cells may play a primary role. An energy-budget model of neural-vascular-glial interaction is provided together with an equivalent electrical circuit that accounts for the results.