PubMed Health⌕ Search

Biomedical subjects

Ido Perlman

Publications and source records attributed to Ido Perlman.

15 recordsLinked to original sources
PubMed2007

Evaluation of intravitreal kenalog toxicity in humans.

OBJECTIVE: To evaluate possible functional toxicity of intravitreal Kenalog (commercial triamcinolone acetonide) in patients' retinas. DESIGN: Observational case series. PARTICIPANTS: Thirty-two phakic eyes of 16 patients who had nonproliferative diabetic retinopathy and bilateral macular edema refractory to laser therapy, which had no other eye disorder and no previous ophthalmic operation. INTERVENTION: Kenalog (4 mg/0.1 ml) was injected intravitreally to one eye, whereas the second eye served as the control. The experimental eye was chosen as the eye with worse visual acuity (VA). MAIN OUTCOME MEASURES: Deterioration of electroretinogram parameters of the study eye measured at 3 months of follow-up when compared with the electroretinogram responses of the fellow, control eye and when compared with electroretinogram responses obtained before injection. Visual acuity, intraocular pressure (IOP), and eventual complications were assessed. No improvement or deterioration of VA or any increase in IOP was regarded as a secondary outcome. RESULTS: Average maximal response amplitude ratios of the dark-adapted b-wave (treated/control eyes) of the electroretinogram were 0.93 before (P = 0.221) and 0.94 (P = 0.387) 3 months after Kenalog injection. Average ratios of the light-adapted b-wave amplitude (treated/control eyes) of the electroretinogram were 1.04 (P = 0.702) before and 0.86 (P = 0.138) 3 months after Kenalog injection. No significant differences (P>0.05) were found between the electroretinogram parameters obtained from all eyes before and 3 months after Kenalog injection. Average VAs in the treated eyes were 1.08, 0.8, and 1.0 logarithm of the minimum angle of resolution units before and 2 and 4 months after injection, respectively. Temporary elevation of IOP was found in 4 treated eyes of 4 patients (25%). CONCLUSIONS: No electroretinographic evidence of a retinotoxic effect of intravitreal Kenalog was found in our patients.

Adult↗
PubMed2006

Light-induced changes in spike synchronization between coupled ON direction selective ganglion cells in the mammalian retina.

Although electrical coupling via gap junctions is prevalent among ganglion cells in the vertebrate retina, there have been few direct studies of their influence on the light-evoked signaling of these cells. Here, we describe the pattern and function of coupling between the ON direction selective (DS) ganglion cells, a unique subtype whose signals are transmitted to the accessory optic system (AOS) where they initiate the optokinetic response. ON DS cells are coupled indirectly via gap junctions made with a subtype of polyaxonal amacrine cell. This coupling underlies synchronization of the spontaneous and light-evoked spike activity of neighboring ON DS cells. However, we find that ON DS cell pairs show robust synchrony for all directions of stimulus movement, except for the null direction. Null stimulus movement evokes a GABAergic inhibition that temporally shifts firing of ON DS cell neighbors, resulting in a desynchronization of spike activity. Thus, detection of null stimulus movement appears key to the direction selectivity of ON DS cells, evoking both an attenuation of spike frequency and a desynchronization of neighbors. We posit that active desynchronization reduces summation of synaptic potentials at target AOS cells and thus provides a secondary mechanism by which ON DS cell ensembles can signal direction of stimulus motion to the brain.

Action Potentials↗
PubMed2006

Hypotrichosis with juvenile macular dystrophy: clinical and electrophysiological assessment of visual function.

PURPOSE: To evaluate retinal function in subjects suffering from hypotrichosis with juvenile macular dystrophy (HJMD). DESIGN: Retrospective case-control study. PARTICIPANTS: Sixteen HJMD patients belonging to 2 genetic groups and 20 control subjects. METHODS: The HJMD patients underwent clinical ophthalmological examination and electrophysiological testing for a period of as many as 14 years. The electroretinogram (ERG), electro-oculogram (EOG), and visual evoked potential (VEP) were recorded serially to assess visual function and to follow possible progression of the disease. MAIN OUTCOME MEASURES: Amplitudes and implicit times of ERG and VEP, and Arden ratio of EOG. RESULTS: Fundus examination revealed pigmentary abnormalities with atrophic changes at the posterior pole extending to regions beyond the macular area. A slow and time-dependent decline in visual acuity was noted. The ERG responses were subnormal in amplitude. The ERG deficit was similar for light- and dark-adapted responses. There was a gradual but consistent decrease in the ERGs with time. The EOG measurements were within the normal range. Pattern reversal VEPs were very subnormal, even in patients with mild deterioration of visual acuity. The flash VEPs were of slightly subnormal amplitudes and implicit times in the upper limit of the normal range. CONCLUSIONS: The fundus pictures and electrophysiological tests were consistent with retinal involvement extending beyond the macular region. Follow-up of visual acuity and ERG testing indicated a slowly progressing retinal disorder affecting cone-mediated vision as well as rod-mediated vision. Therefore, we suggest that a more appropriate name for this syndrome is hypotrichosis with cone-rod dystrophy.

Adolescent↗
PubMed2006

Electrophysiologic and retinal penetration studies following intravitreal injection of bevacizumab (Avastin).

PURPOSE: Intravitreal bevacizumab (Avastin; Genentech Inc., San Francisco, CA) is a new treatment for age-related macular degeneration. The aim of this study was to evaluate retinal penetration and toxicity of bevacizumab. METHODS: Ten albino rabbits were injected intravitreally with 0.1 mL (2.5 mg) of Avastin into one eye and 0.1 mL saline into the fellow eye. The electroretinogram (ERG) was recorded after 3 hours, 3 days, and 1, 2, and 4 weeks. The visual evoked potential (VEP) was recorded after 4 weeks. Confocal immunohistochemistry was used to assess retinal penetration. RESULTS: The ERG responses of the control and experimental eyes were similar in amplitude and pattern throughout the follow-up period. The flash VEP responses of the experimental eyes were of normal pattern and amplitude and did not differ from those recorded by stimulation of the control eye alone. Full thickness retinal penetration was present at 24 hours and was essentially absent at 4 weeks. CONCLUSIONS: Bevacizumab was found to be nontoxic to the retina of rabbits based on electrophysiologic studies. Full thickness retinal penetration may explain observed clinical effects of intravitreal bevacizumab. Although it is difficult to directly extrapolate to humans, our study supports the safe use of intravitreal bevacizumab injection.

Animals↗
PubMed2006

Retinal toxicity of indocyanine green in albino rabbits.

PURPOSE: Intravitreal indocyanine green (ICG) is commonly used in vitreoretinal surgery. The purpose of this study was to evaluate possible toxicity of ICG in the retina of albino rabbits. METHODS: Twenty-two albino rabbits were injected intravitreally with 0.1 mL ICG solution in one eye, and three rabbits were studied for the effects of 0.1 mL distilled water. All rabbits were injected intravitreally with 0.1 mL saline into the fellow eye, which served as the control. The electroretinogram (ERG) and visual evoked potential (VEP) were recorded from each rabbit at different time intervals after injection. The rabbits were killed at the termination of the follow-up periods and their retinas prepared for histologic examination at the light microscopic level. RESULTS: Three hours after injection, the ERG responses were reduced in amplitude in all ICG-injected eyes, and the VEPs were of abnormal pattern (reduced amplitude and delayed). Partial dose-dependent recovery was observed during 4 weeks of follow-up. Light microscopy of the retinas of the experimental eyes exhibited considerable damage to all retinal layers in all eyes studied that received the highest ICG dose. CONCLUSIONS: ICG is potentially toxic to all retinal layers of the albino rabbit. Although it is difficult to extrapolate these findings directly to human eyes, caution should be exercised when using ICG intravitreally.

Animals↗
PubMed2005

Altered membrane physiology in Müller glial cells after transient ischemia of the rat retina.

Inwardly rectifying K+ (Kir) channels have been implicated in the mediation of retinal K+ homeostasis by Muller glial cells. To assess possible involvement of altered glial K+ channel expression in ischemia-reperfusion injury, transient retinal ischemia was induced in rat eyes. Acutely isolated Muller cells from postischemic retinae displayed a fast downregulation of their Kir currents, which began within 1 day and reached a maximum at 3 days of reperfusion, with a peak decrease to 20% as compared with control. This strong decrease of Kir currents was accompanied by an increase of the incidence of cells which displayed depolarization-evoked fast transient (A-type) K+ currents. While no cell from untreated control rats expressed A-type K+ currents, all cells investigated from 3- and 7-day postischemic retinae displayed such currents. An increased incidence of cells displaying fast transient Na+ currents was observed at 7 days after ischemia. These results suggest a role of altered glial Kir channel expression in postischemic neuronal degeneration via disturbance of retinal K+ siphoning.

Animals↗
PubMed2004

Mechanism of spontaneous excitability in human embryonic stem cell derived cardiomyocytes.

Human embryonic stem cell-derived cardiomyocytes (hES-CMs) are thought to recapitulate the embryonic development of heart cells. Given the exciting potential of hES-CMs as replacement tissue in diseased hearts, we investigated the pharmacological sensitivity and ionic current of mid-stage hES-CMs (20-35 days post plating). A high-resolution microelectrode array was used to assess conduction in multicellular preparations of hES-CMs in spontaneously contracting embryoid bodies (EBs). TTX (10 microm) dramatically slowed conduction velocity from 5.1 to 3.2 cm s(-1) while 100 microm TTX caused complete cessation of spontaneous electrical activity in all EBs studied. In contrast, the Ca2+channel blockers nifedipine or diltiazem (1 microm) had a negligible effect on conduction. These results suggested a prominent Na+ channel current, and therefore we patch-clamped isolated cells to record Na+ current and action potentials (APs). We found for isolated hES-CMs a prominent Na+ current (244 +/- 42 pA pF(-1) at 0 mV; n=19), and a hyperpolarization-activated current (HCN), but no inward rectifier K+ current. In cell clusters, 3 microm TTX induced longer AP interpulse intervals and 10 microm TTX caused cessation of spontaneous APs. In contrast nifedipine (Ca2+ channel block) and 2 mm Cs+ (HCN complete block) induced shorter AP interpulse intervals. In single cells, APs stimulated by current pulses had a maximum upstroke velocity (dV/dtmax) of 118 +/- 14 V s(-1) in control conditions; in contrast, partial block of Na+ current significantly reduced stimulated dV/dtmax (38 +/- 15 V s(-1)). RT-PCR revealed NaV1.5, CaV1.2, and HCN-2 expression but we could not detect Kir2.1. We conclude that hES-CMs at mid-range development express prominent Na+ current. The absence of background K+ current creates conditions for spontaneous activity that is sensitive to TTX in the same range of partial block of NaV1.5; thus, the NaV1.5 Na+ channel is important for initiating spontaneous excitability in hES-derived heart cells.

Action Potentials↗
PubMed2004

Homogeneity and diversity of color-opponent horizontal cells in the turtle retina: Consequences for potential wavelength discrimination.

Color information processing in fish and turtles starts with the transformation of the tetra-chromatic cone system into two types of color-opponent horizontal cells (C-type). Few studies reported on large variability between C-type horizontal cells of the same class, suggesting it might improve color vision. However, such variability is contradictory with the tight coupling between horizontal cells that tends to average intercellular differences. We addressed this apparent discrepancy, and studied the spectral properties of C-type horizontal cells in the turtle retina. Photoresponses were recorded in the eyecup preparation, using light stimuli of different wavelengths and intensities. The spectral properties of each cell were defined by the neutral points (wavelengths at which response polarity reversed), which were derived from sensitivity data and from large-amplitude photoresponses. For each C-type horizontal cell, a linear relationship between log stimulus intensity needed for polarity reversal and wavelength was found. With this definition, homologous C-type horizontal cells from the same retina were practically identical in their spectral properties, indicating that the averaging effects of the horizontal cell syncytium eliminated any intercellular variability. In contrast, C-type horizontal cells of the same class exhibited large inter-retina variability. We tested the potential for wavelength discrimination by applying the line element theory to the action spectra of the two chromatic (Red/Green & Yellow/Blue) horizontal cell channels, and found good agreement with behavioral data from a similar species of turtles.

Animals↗
PubMed2004

Effect of defocusing and of distracted attention upon recordings of the visual evoked potential.

Pattern reversal visual stimuli are used to evoke potentials (VEPs) for assessment of visual acuity and for localizing defects along the visual pathways. Our goal was to assess the importance of attention and defocusing to the recordings of pattern VEP. Forty-one volunteers with normal (6/6) corrected visual acuity participated in this study. Twenty-one were asked to defocus intentionally the visual stimulus (located 200 cm away) by fixating at a target 25 or 50 cm from the eye. Twenty other subjects performed auditory tasks to distract their attention from the visual stimulus. Pattern VEPs were elicited by different check sizes. The amplitude and time-to-peak of the P100 wave were measured. Intentional defocusing caused amplitude reduction and prolongation of the time-to-peak in young subjects (20-34 years old). With the smallest checks used (7.5') we could not record a reliable response from 43% of the young subjects (6 out of 14). In older patients (35-61 years old), intentional defocusing induced negligible effects on pattern VEPs regardless of check size. There were no effects of auditory distraction upon the pattern VEPs. Our data suggest that intentional defocusing can produce false positive results (reduced VEP with prolonged time-to-peak) only when small checks are used in young subjects. Divided attention has negligible effect on the recordings of pattern VEPs. With proper controls, the pattern VEP test can be used for objective assessment of visual function.

Adult↗
PubMed2003

Contribution of connexin26 to electrical feedback inhibition in the turtle retina.

The first synaptic integration in the neuronal cascade of vision in vertebrates includes a feedback from horizontal cells to cones by a mechanism yet not fully understood. Recent observations in teleosts suggested an electrical feedback mechanism mediated by connexin26 (Cx26) hemichannels at the terminal dendrites of horizontal cells. By using reverse transcription-polymerase chain reaction and immunoblotting from retinal homogenate, we detected Cx26 mRNA transcripts in the turtle retina and demonstrated that they were translated into protein. Cx26 immunoreactivity was especially prominent in the outer plexiform layer. Subcellularly, immunoreactivity was located mainly between horizontal cell axon terminals and in horizontal cell dendrites forming the lateral elements at the ribbon synaptic complex of the cone pedicle. The label was confined to the horizontal cell membrane flanking the ribbon and was not found on the opposing photoreceptor membrane. No gap junctions at this location are known, so immunosignaling suggested the presence of hemichannels. Their relevance to the feedback mechanism was investigated by intracellular recordings from horizontal cells during application of the hemichannel blocker carbenoxolone. Carbenoxolone hyperpolarized the dark membrane potential by about 25 mV, decreased the amplitudes of responses to full-field light flashes, and suppressed the feedback-induced depolarizing inflexion in the response profile. These physiological findings are compatible with the involvement of hemichannels in the feedback between horizontal cells and cones and support the anatomical findings. Together, these data suggest the presence of an electrical feedback mechanism in the turtle retina, which therefore might be a common mechanism at the first visual synapse in vertebrates.

Animals↗
PubMed2003

NADPH diaphorase activity in the rat retina during the early stages of experimental diabetes.

BACKGROUND: Nitric oxide (NO) plays an important physiological role in inter-cellular communication, but when produced in excess it can become toxic. Our goal was to evaluate possible involvement of NO in the development of retinopathy in diabetic rats. METHODS: Diabetes was induced in male albino rats by intravenous injection of streptozotocin. Some of the normal and diabetic rats were raised with added L-arginine to increase in vivo NO synthesis, or with added L-NAME to inhibit the rate of in vivo NO synthesis. NADPH diaphorase histochemistry was conducted on retinal whole mounts and transverse sections at different time intervals after induction of diabetes. The electroretinogram (ERG) was recorded to assess retinal function. RESULTS: After 6 weeks of diabetes, NADPH diaphorase amacrine cells in the diabetic retinas appeared abnormal in their morphology and the degree of staining was decreased in their processes. In contrast, NADPH diaphorase activity was augmented in Müller cells. Supplementing the rats' diet with L-arginine for 10 weeks slightly reduced NADPH diaphorase activity in amacrine cell in normal rats but had no effect on the diabetic rats. Adding L-NAME for 10 weeks did not alter NADPH diaphorase histochemistry in either normal or diabetic rats. The ERG responses were reduced by L-arginine supplementation in normal and diabetic rats, and were unaffected by adding L-NAME to the drinking water. CONCLUSIONS: Our findings are consistent with the hypothesis that high glucose levels are deleterious to the rat retina and that excessive synthesis of NO may contribute to the development of diabetic retinopathy.

Animals↗
PubMed2003

Color opponency in horizontal cells of the vertebrate retina.

Chromaticity (C-type) horizontal cells have been studied extensively for more than 40 years since the first recording of such units in the fish retina. C-type horizontal cells are seen in almost every retina of cold-blooded species that contains at least two different spectral types of cone. These cells are characterized by photoresponses of polarity that depends upon the wavelength of the stimulating light. There are two basic varieties of chromaticity horizontal cells, biphasic or triphasic cells. Biphasic cells are characterized by one wavelength in which response polarity reverses and triphasic cells have two wavelengths where response polarity reverses. The neuronal network underlying the genesis of color opponency in C-type horizontal cells has been the subject of debate for many years. It is generally accepted now that cones feed-forward excitatory inputs to horizontal cells which in turn exert inhibitory effects on the cones by negative feedback pathways. C-type horizontal cells belonging to the same class are interconnected via gap junctions to form a tight syncytium. However, the spatial properties of these cells depend upon the polarity of the photoresponse because the membrane resistances of the syncytium change with different inputs. Thus, color opponency in C-type horizontal cells depends on the spatial properties of the stimulating light in addition to its dependence upon wavelength, intensity and ambient illumination. The functional role of C-type horizontal cells is to influence the spatial-chromatic organization of the receptive fields of proximal neurons. Thus, the responsiveness of bipolar cells and ganglion cells to surround illumination depend to a great extent upon the horizontal cells. However, the exact mode whereby horizontal cells can affect the organization of the proximal neurons has yet to be elucidated.

Animals↗
PubMed2003

Functional damage to inner and outer retinal cells in experimental glaucoma.

PURPOSE: To investigate the cellular sources underlying the functional damage observed by multifocal electroretinography (mfERG) responses of glaucomatous eyes of monkeys. METHODS: First- and second-order (K1 and K2, respectively) mfERG responses of three normal and three experimentally induced glaucomatous eyes of cynomolgus monkeys were measured at two different levels of luminance. Retinal contributors to the responses were isolated by intravitreal injections of pharmacological agents that suppress specific retinal cells. gamma-Aminobutyric acid (GABA) and glycine were administered to block inner retinal function, followed by 2-amino-4-phosphonobutyric acid (APB), to block ON-bipolar cells. RESULTS: An inner retinal component removed by GABA and glycine was found in both the normal and glaucomatous eyes. However, it was attenuated in the latter, correlating with changes observed in the baseline K1 responses. Delays in the latency of outer retinal components were found in the responses of the glaucomatous eyes. K2 responses were dominated by an inner retinal contribution and were diminished in the responses of glaucomatous eyes. The outer retina responded to increased luminance with a shorter implicit time. A distinct wave part of the inner retinal component responded to increased luminance with increased amplitudes. CONCLUSIONS: The integration of the retinal sources forming the mfERG response was compared between normal and glaucomatous monkey eyes. Both inner and outer retinal functions were aberrant in the responses of the glaucomatous eyes, with the attenuation of the inner retinal function more conspicuous. Nevertheless, glaucomatous eyes retained certain inner retinal activity, despite the advanced stage of disease. K2 responses were more sensitive to glaucomatous changes than were K1 responses.

Aminobutyrates↗
PubMedDate not supplied

Light adaptation and color opponency of horizontal cells in the turtle retina.

Chromaticity-type (C-type) horizontal cells of the turtle retina receive antagonistic inputs from cones of different spectral types, and therefore their response to background illumination is expected to reflect light adaptation of the cones and the interactions between their antagonistic inputs. Our goal was to study the behavior of C-type horizontal cells during background illumination and to evaluate the role of wavelength in background adaptation. The photoresponses of C-type horizontal cells were recorded intracellularly in the everted eyecup preparation of the turtle Mauremys caspica during chromatic background illuminations. The voltage range of operation was either reduced or augmented, depending upon the wavelengths of the background and of the light stimuli, while the sensitivity to light was decreased by any background. The response-intensity curves were shifted to brighter intensities and became steeper as the background lights were made brighter regardless of wavelength. Comparing the effects of cone iso-luminant backgrounds on the Red/Green C-type horizontal cells indicated that background desensitization in these cells could not solely reflect background adaptation of cones but also depend upon response compression/expansion and changes in synaptic transmission. This leads to wavelength dependency of background adaptation in C-type horizontal cells, that is expressed as increased light sensitivity (smaller threshold elevation) and improved suprathreshold contrast detection when the wavelengths of the background and light stimuli were chosen to exert opponent effects on membrane potential.

Adaptation, Ocular↗