Riluzole improves functional recovery after ischemia in the rat retina.
(1/2711)
PURPOSE: Retinal ischemia leads to neuronal death. The effects of riluzole, a drug that protects against the deleterious effect of cerebral ischemia by acting on several types of ion channels and blocking glutamatergic neurotransmission, were investigated in a rat model of retinal ischemic injury. METHODS: Retinal ischemia was induced by increasing intraocular pressure above systolic blood pressure for 30 minutes. Electroretinograms were recorded before ischemia and at different periods of reperfusion. Riluzole was injected or topically applied to the eye before or after ischemia and twice daily during the reperfusion period. Retinas were harvested for histopathology (toluidine blue and silver-impregnation stainings, Tdt-dUTP terminal nick-end labeling [TUNEL] method) and immunohistochemistry for cytoskeletal glial fibrillary acid protein and c-jun NH2-terminal kinase (p-JNK). RESULTS: Ischemia for 30 minutes caused a reduction of a- and b-waves of the electroretinogram. Systemic and topical treatments with riluzole significantly enhanced the recovery of the reduced a- and b-waves after defined reperfusion times. Riluzole also prevented or attenuated ischemia-induced retinal cell death (necrosis and apoptosis) and reduced the activation of p-JNK, c-jun phosphorylation, and the increase of cytoskeletal proteins induced by ischemic injury. CONCLUSIONS: Riluzole acted in vivo as a potent neuroprotective agent against pressure-induced ischemia. Therefore, riluzole may be a major drug for use in protection against retinal injury. (+info)
Formate-induced inhibition of photoreceptor function in methanol intoxication.
(2/2711)
Formic acid is the toxic metabolite responsible for the retinal and optic nerve toxicity produced in methanol intoxication. Previous studies in our laboratory have documented formate-induced retinal dysfunction and histopathology in a rodent model of methanol intoxication. The present studies define the time and concentration dependence of formate-induced retinal toxicity in methanol-intoxicated rats. Retinal function was assessed 24, 48, and 72 h after the initial dose of methanol by flicker electroretinographic measurements. Retinal histopathology was assessed at the same time intervals. Rod- and cone-mediated electroretinogram (ERG) responses were attenuated in a formate concentration- and time-dependent manner, and both retinal sensitivity and maximal responsiveness to light were diminished. Attenuation of UV-cone-mediated responses was temporally delayed in comparison to the functional deficits observed in the 15 Hz/510 nm responses, which have a rod-mediated component and occurred at significantly higher formate concentrations. Both 15 Hz/510 nm and UV-cone-mediated ERG responses were undetectable by 72 h; however, if light intensity was increased, a retinal ERG response could be recorded, indicating that photoreceptor function was profoundly attenuated, but not abolished, under these intoxication conditions. Functional changes preceded structural alterations. Histopathological changes were most pronounced in the outer retina with evidence of inner segment swelling, photoreceptor mitochondrial disruption, and the appearance of fragmented photoreceptor nuclei in the outer nuclear layer. The nature of both the functional and structural alterations observed are consistent with formate-induced inhibition of mitochondrial energy production, resulting in photoreceptor dysfunction and pathology. (+info)
Sensitivity and kinetics of mouse rod flash responses determined in vivo from paired-flash electroretinograms.
(3/2711)
1. Electroretinograms (ERGs) were recorded corneally from C57BL/6J mice using a paired-flash procedure in which a brief test flash at time zero was followed at time tprobe by a bright probe flash of fixed strength, and in which the probe response amplitude was determined at time t = tprobe + 6 ms. Probe responses obtained in a series of paired-flash trials were analysed to derive A(t), a family of amplitudes that putatively represents the massed response of the rod photoreceptors to the test flash. A central aim was to obtain a mathematical description of the normalized derived response A(t)/Amo as a function of Itest, the test flash strength. 2. With fixed tprobe (80 <= tprobe <= 1200 ms), A(t)/Amo was described by the saturating exponential function [1 - exp(-ktItest)], where kt is a time-dependent sensitivity parameter. For t = 86 ms, a time near the peak of A(t), k86 was 7.0 +/- 1.2 (scotopic cd s m-2)-1 (mean +/- s. d.; n = 4). 3. A(t)/Amo data were analysed in relation to the equation below, a time-generalized form of the above exponential function in which (k86Itest) is replaced by the product [k86Itestu(t)], and where u(t) is independent of the test flash strength. The function u(t) was modelled as the product of a scaling factor gamma, an activation term 1 - exp[-alpha(t - td)2]), and a decay term exp(-t/tauomega): A(t)/Amo = 1 - exp[-k86Itestu(t)]; u(t) = gamma(1 - exp[-alpha(t - td)2](exp(-t/tauomega) where td is a brief delay, tauomega is an exponential time constant, and alpha characterizes the acceleration of the activation term. For Itest up to approximately 2.57 scotopic cd s m-2, the overall time course of A(t) was well described by the above equation with gamma = 2.21, td = 3.1 ms, tauomega = 132 ms and alpha = 2.32 x 10-4 ms-2. An approximate halving of alpha improved the fit of the above equation to ERG a-wave and A(t)/Amo data obtained at t about 0-20 ms. 4. Kinetic and sensitivity properties of A(t) suggest that it approximates the in vivo massed photocurrent response of the rods to a test flash, and imply that u(t) in the above equation is the approximate kinetic description of a unit, i.e. single photon, response. (+info)
Cone signal contributions to electroretinograms [correction of electrograms] in dichromats and trichromats.
(4/2711)
PURPOSE: To find out how the different cone types contribute to the electroretinogram (ERG) by quantifying the contribution of the signal pathways originating in the long (L-) and the middle (M-) wavelength-sensitive cones to the total ERG response amplitude and phase. METHODS: ERG response amplitudes and phases were measured to cone-isolating stimuli and to different combinations of L- and M-cone modulation. Conditions were chosen to exclude any contribution of the short wavelength-sensitive (S-) cones. The sensitivity of the ERG to the L and the M cones was defined as the cone contrast gain. RESULTS: In the present paper, a model is provided that describes the ERG contrast gains and ERG thresholds in dichromats and color normal trichromats. For the X-chromosome-linked dichromats, the contrast gains of only one cone type (either the L or the M cones) sufficed to describe the ERG thresholds for all stimulus conditions. Data suggest that the M-cone contrast gains of protanopes are larger than the L-cone contrast gains of deuteranopes. The response thresholds of the trichromats are modeled by assuming a vector summation of signals originating in the L and the M cones. Their L- and M-cone contrast gains are close to a linear interpolation of the data obtained from the dichromats. Nearly all trichromats had larger L- than M-cone contrast gains. Data from a large population of trichromats were examined to study the individual variations in cone weightings and in the phases of the cone pathway responses. CONCLUSIONS: The data strongly suggest that the missing cone type in dichromats is replaced by the remaining cone type. The mean L-cone to M-cone weighting ratio in trichromats was found to be approximately 4:1. But there is a substantial interindividual variability between trichromats. The response phases of the L- and the M-cone pathways can be reliably quantified using the response phases to the cone-isolating stimuli or using a vector addition of L- and M-cone signals. (+info)
Hypersensitivity in the anterior median eye of a jumping spider.
(5/2711)
Changes in sensitivity of the photoreceptor cells of the anterior median eye of the jumping spider Menemerus confusus Boes. et Str. have been studied by recording electroretinograms (ERGs) and receptor potentials. The amplitudes of the responses (ERGs and receptor potentials) increase during repetitive stimulation, with a maximum increase at 3-5 s intervals. The sensitivity of the photoreceptor cell is greater for about 60 s following illumination (maximum magnitude at 3-5 s) than it is during complete dark adaptation. This phenomenon, which we call 'hypersensitivity', is lost within one day following surgery in physiological saline. Upon loss of hypersensitivity, the sensitivity decrease during light adaptation is greater than for the normal eye and the small increase of sensitivity following the onset of illumination observed for the normal eye is lost. (+info)
Human cone pigment expressed in transgenic mice yields altered vision.
(6/2711)
Genetically driven alterations in the complement of retinal photopigments are fundamental steps in the evolution of vision. We sought to determine how a newly added photopigment might impact vision by studying a transgenic mouse that expresses a human cone photopigment. Electroretinogram (ERG) measurements indicate that the added pigment works well, significantly changing spectral sensitivity without deleteriously affecting the operation of the native cone pigments. Visual capacities of the transgenic mice were established in behavioral tests. The new pigment was found to provide a significant expansion of the spectral range over which mice can perceive light, thus underlining the immediate utility of acquiring a new photopigment. The transgenic mouse also has the receptor basis for a novel color vision capacity, but tests show that potential was not realized. This failure likely reflects limitations in the organizational arrangement of the mouse retina. (+info)
Mid-peripheral pattern electrical retinal responses in normals, glaucoma suspects, and glaucoma patients.
(7/2711)
AIMS: Reliance on intraocular pressure, optic nerve cupping changes, nerve fibre layer integrity, and visual field changes may delay treatment of glaucoma since irreversible changes may have already occurred at the time of diagnosis. Abnormal pattern electrical retinal responses (PERR or PERG) have been demonstrated in patients with ocular hypertension (no visual field changes) and glaucoma when visual stimulation was presented to the central field. Since glaucomatous visual field changes tend to occur first in the mid-periphery, the use of PERR outside of the central field may offer an earlier indication of glaucomatous involvement. METHODS: Glaucoma suspects and glaucoma patients were derived from a university practice. Normal subjects were recruited from non-patient volunteers. Alternating bar gratings were presented in the supranasal, supratemporal, infratemporal, and infranasal visual field. Six spatial frequencies, from 0.25 to 6.0 cycles per degree, were used for normal volunteers; three spatial frequencies, from 0.38 to 1.5 cycles per degree, were presented to suspects and glaucoma patients. Time of onset of the first negative (N35) and first positive peak (P50) and the amplitude consisting of the absolute difference between the first negative peak and first positive peak (P50 amplitude) are reported. Age corrected values were determined for normals, suspects, and glaucoma patients for each spatial frequency and for each quadrant in the visual field. RESULTS: Mean P50 amplitudes from normal subjects showed spatial tuning in all quadrants with reduced low frequency attenuation. Normals demonstrated a small decline in amplitude with age. Glaucoma patients demonstrated an age corrected reduction in amplitude and early implicit times. Glaucoma suspects had values between those of normal and glaucoma subjects. P50 amplitudes were weakly correlated with increasing cup to disc diameter ratio. A glaucoma patient with asymmetric visual field loss demonstrated significant diminution of the PERR bilaterally. CONCLUSION: The PERR, using mid-peripheral stimulation, may be a sensitive tool for the early detection of glaucoma. Further refinements can speed clinical data acquisition and enhance signal to noise ratio. (+info)
ERG phenotype of a dystrophin mutation in heterozygous female carriers of Duchenne muscular dystrophy.
(8/2711)
PURPOSE: Mutations in the dystrophin gene result in Duchenne muscular dystrophy (DMD). DMD is associated with an abnormal electroretinogram (ERG) if the mutation disrupts the translation of retinal dystrophin (Dp260). Our aim was to determine if incomplete ERG abnormalities would be associated with heterozygous carriers of dystrophin gene mutations. METHODS: Ganzfeld ERGs were obtained under scotopic and photopic testing conditions from a family which includes the heterozygous maternal grandmother, the heterozygous mother, and her children, two affected boys and dizygotic twin sibs, an unaffected male and heterozygous female. Southern blot analyses were done to characterise the dystrophin mutation. RESULTS: The dystrophin gene was found to contain a deletion encompassing exon 50. The ERGs in the two affected boys were abnormal, consistent with the DMD ERG phenotype. Serial ERGs of the heterozygous females were abnormal; however, they were less severely affected than the DMD boys. The ERG of the female sib showed a greater abnormality than her mother and maternal grandmother. The unaffected twin had a normal ERG. CONCLUSIONS: The ERG shows abnormalities associated with carrier status in this family with a single exon deletion. A large study of confirmed obligate carriers is planned to clarify further the value of the ERG in detecting female heterozygous carriers of dystrophin gene mutations. (+info)