Photopic Electroretinogram Research Articles

The Protein Kinase DYRK1A Regulates Caspase-9-Mediated Apoptosis during Retina Development

The precise regulation of programmed cell death is critical for the normal development of the nervous system. We show here that DYRK1A (minibrain), a protein kinase essential for normal growth, is a negative regulator of the intrinsic apoptotic pathway in the developing retina. We provide evidence that changes in Dyrk1A gene dosage in the mouse strongly alter the cellularity of inner retina layers and result in severe functional alterations. We show that DYRK1A does not affect the proliferation or specification of retina progenitor cells, but rather regulates the number of cells that die by apoptosis. We demonstrate that DYRK1A phosphorylates caspase-9 on threonine residue 125, and that this phosphorylation event is crucial to protect retina cells from apoptotic cell death. Our data suggest a model in which dysregulation of the apoptotic response in differentiating neurons participates in the neuropathology of diseases that display DYRK1A gene-dosage imbalance effects, such as Down's syndrome.

Light responses in the mouse retina are prolonged upon targeted deletion of the HCN1 channel gene

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels contribute to pacemaker activity, and co-determine the integrative behaviour of neurons and shape their response to synaptic stimulation. Four channel isoforms, HCN1-4, have been described in mammals. Recent studies showed particularly strong expression of HCN1 channels in rods and cones of the rat retina, suggesting that HCN1 channels are involved in the shaping of light responses in both types of photoreceptors. Therefore, the loss of HCN1 channels should lead to pronounced changes in light-induced electrical responses under both scotopic and photopic conditions. This was tested using a mouse transgenic approach. We used immunohistochemistry and patch-clamp recording to study the distribution of HCN1 channels in the mouse retina. HCN1 channels were strongly expressed in rod and cone photoreceptors, as well as in some bipolar, amacrine and ganglion cell types. In electroretinograms (ERGs) from animals in which the HCN1 channel gene had been knocked out, the b-wave amplitudes were unaltered (scotopic conditions) or somewhat reduced (photopic conditions), whereas the duration of both scotopic and photopic ERG responses was strikingly prolonged. Our data suggest that in visual information processing, shortening and shaping of light responses by activation of HCN1 at the level of the photoreceptors is an important step in both scotopic and photopic pathways.

A negative electroretinogram (ERG) in a case of probable multiple system atrophy (MSA)

Recent articles have described negative ERGs in a small number of patients with cerebellar degeneration. Five of the previously reported seven cases were hereditary (2/5 had spinocerebellar ataxia-1 (SCA-1) gene mutations) and the other two were sporadic. We report a negative ERG in a case of cerebellar degeneration that differs significantly from earlier cases. The 65-year-old man had a 5-year history of ataxia, unsteady gait, orthostatic hypotension, and bladder and erectile dysfunction, with no family history of neurological or retinal disease. Visual acuity was 20/30 OD, 20/40 OS, but reportedly was never 20/20. His fundus exam showed optic nerve pallor, but otherwise was normal. Visual fields had enlarged blind spots but no central scotomas. Autofluorescence was normal. Photopic flash and 30-Hz ERG responses were normal. Rod b-waves were reduced and delayed. Standard flash a-waves were normal, but the b-waves were smaller than the a-waves. Blood tests were negative for Leber's hereditary optic neuropathy, dominant optic atrophy, and for expansions in SCA genes including SCA-1. This is only the third reported case of sporadic ataxia with a negative ERG. The patient's prominent autonomic dysfunction differs from the previous cases, and meets the clinical criteria for probable multiple system atrophy (MSA). This introduces another possible diagnosis in cases of negative ERGs with ataxia, and suggests that the visual system may be affected in MSA.

ERG findings in three hypothyroid adult dogs with and without levothyroxine treatment

To evaluate the effects of levothyroxine (LTh) on the electroretinogram (ERG) of adult dogs. Binocular, full field photopic and scotopic ERGs were recorded from an anesthetized Maltese Bichon cross (MB), a Yorkshire Terrier (YT) and a Shetland Sheepdog (SS) affected with hypothyroidism and treated with a daily dose of LTh at 20 microg/kg. The photopic ERGs were evoked to 12 different intensities ranging from 0.81 to -2.19 log cd.s/m(2) and presented under photopic conditions in order to assess (from the derived luminance-response curves) Vmax and b : a amplitude ratio parameters. Photopic flicker ERGs were obtained at 30 Hz. The scotopic ERGs (intensity: -3.09 log cd.s/m(2)) were recorded while the retina was dark-adapting and after 32 min of dark adaptation. This procedure was performed on two separate sessions: following a 3-day interruption of LTh treatment (S1) and following 30 days without interruption of LTh treatment (S2). The mean photopic a-wave peak times were 9.8 ms at S1 and 5.0 ms at S2, respectively. The mean photopic b-wave peak times were 23.3 ms at S1 and 11.5 ms at S2, respectively, and the mean scotopic b-wave peak times (after 32 min of dark adaptation) were 45.2 ms at S1 and 26.0 ms at S2, respectively. No other significant ERG changes were observed. Our results indicate that a dose of 20 microg/kg of LTh given to adult dogs was accompanied by a marked peak time shortening of both photopic and scotopic ERGs, without affecting other ERG parameters.

Asymmetry of focal macular photopic negative responses (PhNRs) in monkeys

The photopic negative response (PhNR) is a slow, negative-going wave of the photopic electroretinogram (ERG) that appears after the b-wave. Recent studies have shown that the PhNR originates from the spiking activities of inner retinal neurons including the ganglion cells and their axons. The aim of this study was to determine whether there is any asymmetry in the amplitude of the PhNR elicited from the upper and lower macular areas, and between the nasal and temporal macular areas in rhesus monkeys. To accomplish this, we recorded focal macular PhNRs that were elicited by red hemi-circular stimuli presented on a blue background. We show that the PhNR from the upper macular area was significantly larger than that of the lower macular area, and the PhNR of the nasal macula was significantly larger than that of the temporal macula. These asymmetries were present in the focal PhNR elicited by both brief and long duration stimuli, and the asymmetries were completely eliminated by an intravitreal injection of tetrodotoxin (TTX). These results suggest that the upper–lower and nasal-temporal asymmetries of PhNR in the primate retina are mainly caused by TTX-sensitive spiking activities of inner retinal neurons.

The effect of broadband and monochromatic stimuli on the photopic negative response of the electroretinogram in normal subjects and in open-angle glaucoma patients

The aim was to investigate the effects of monochromatic and broadband stimuli on the amplitude of the photopic negative response (PhNR) and to compare the sensitivities of these stimuli for the detection of ganglion cell damage in glaucoma patients. Forty-one healthy subjects were studied, along with 16 patients with open-angle glaucoma. Photopic electroretinograms (ERGs) were elicited with monochromatic red, amber, green, and broadband white stimuli of progressively brighter intensities in a blue background. Pattern ERGs were also recorded using a 0.8 degrees checkerboard pattern on a 21.6 degrees x 27.8 degrees screen. In the photopic ERGs of the control subjects, the PhNR amplitude was significantly higher (P < 0.01) to red than to monochromatic amber, green, and broadband white stimuli of the same intensity. In glaucoma patients, the percentage of amplitude reduction was greater for the PhNR to red (68%, P < 0.001) than to the broadband stimulus (38%, P = 0.001). The PhNR to red monochromatic stimulus appeared to be a more sensitive parameter, with a larger area enclosed by the receiver-operating characteristic curve (0.97) than for the PhNR to broadband stimulus (0.76). Also, the PhNR to red stimulus showed a more significant correlation with the pattern ERG and the visual field defects (P < 0.05) than the PhNR elicited with broadband stimulus. These findings suggest that ganglion cell activity can be more efficiently evaluated with the PhNR elicited with a red than with a broadband stimulus. The PhNR thus appears to be a promising test for the diagnostics of the ganglion cell dysfunction.

Improving the diagnostic potential of the photopic electroretinogram (ERG) with refined mathematical tools

Abstract Purpose Examine if the use of refined mathematical tools increases the understanding and diagnostic potential of the photopic ERGs. Methods Analyses were performed on normal and pathological photopic ERGs (background of 30 cd.m‐2; flash intensities ranging from ‐0.8 to 2.84 log cd.sec.m‐2 in 15 steps; n&gt;100). Mathematical instruments included: 1‐ the Continuous Wavelet Transform (CWT)2‐ The Reiman Integrator and 3‐ the Photopic Hill Gaussian:Logistic ratio [GL=Gb/(Gb+Vbmax)]claimed to weight the contribution of the OFF and ON pathways to the photopic ERG. Results 1‐ CWT revealed 3 distinct frequency domains within the 10‐50 msec poststimulus time interval, namely: 20‐40 Hz, 90‐150 Hz and 200‐300 Hz that appeared to be independently modulated by flash intensity and/or pathology. 2‐ Integration of the OPs accurately reconstructed the broadband ERGs (r&gt;0.90), irrespective of CWT. 3‐ In our cohort of RP patients (n=50), the GL ratio was 0.43 ±0.23, compared to 0.60±0.08 in normal (p&lt;.05). Conclusion 1‐CWT dissects the ERG into its primary components, a method that should allow a more accurate quantification of ERG responses. 2‐ Strong evidence supports the concept that the b‐wave results from the integration of the OPs. The value of the integration constant (1 sec) is close to the time constant of the Muller cell membrane suggesting that the latter could be at the origin of this integration. 3‐The broader GL distribution obtained from our RP cohort suggests that in some the OFF retinal pathway is primarily affected while in others the ON is. It remains to be determined if the latter represents two stages of the same disease process or two different disease paths. Supported by CIHR and Réseau Vision.

The effect of topical anesthesia on the rat electroretinogram

Topical anesthetics are recommended when electroretinograms (ERGs) are recorded using contact lens electrodes. However, these drugs act by blocking voltage-gated Na+ channels. Since such channels have been located in both the inner and outer retina of many species, topical anesthesia could affect the ERG recordings in these subjects. The purpose of this study was to evaluate the effects of oxybuprocaine, a commonly used ester local anesthetic, on the rat ERG. Full-field scotopic and pattern ERGs (PERGs) were recorded successively from both eyes of seven rats. One eye was randomly treated with oxybuprocaine 15 min prior to recording. In 10 rats unilateral full-field photopic ERG recordings were conducted prior to, and 15 min after, treatment. B-wave amplitude ratios of the experimental/control eyes were 1.13, 1.30, and 1.35 for the three intensities used to record scotopic ERG responses, and 1.04 for the photopic ERG responses. PERG amplitude ratios of the experimental/control eyes were 1.10, 1.21, 1.21, 1.24, and 1.26 for the five patterns used. Treatment had no significant negative effect on signal amplitude or implicit time of the full-field ERG or PERG. In fact, amplitudes of signals from treated eyes tended to be (insignificantly) higher, though this might reflect better position of the active electrode rather than a biological effect. We conclude that oxybuprocaine has no negative effect on the rat ERG.

Modulation of ERG retinal sensitivity parameters with light environment and photoperiod

It has been reported that the sensitivity to light of the circadian system of animals and human subjects can be modulated following long-term exposure to a given light environment. Animal studies have also shown that long-term exposure to a light regimen, or light history, will have a significant impact on the retinal structure and function, the objective of which being to regulate the number of photons processed daily by the retina, a phenomenon referred to as photostasis. The existence of such a mechanism has never been explored in humans. In the present study, daily light exposure was continuously recorded in two populations of full-time workers: one group working indoors, in a relatively dim environment without access to natural light, and one group working mainly outdoors in natural bright light. The effect of seasonal changes in the length of the photoperiod was also examined. Retinal sensitivity, as determined with scotopic and photopic electroretinograms (ERG), was compared between these two groups. Indoor workers received less light than outdoor workers, the difference being significant only during work hours. A dim work environment was associated with greater retinal sensitivity in scotopic conditions and lower retinal sensitivity in photopic conditions when compared to a bright work environment. The above differences in retinal sensitivity were evidenced only in workers studied during the months with the shortest photoperiod (Fall-Winter). These results support the hypothesis that, similar to what was previously demonstrated with animal models, the human retina adapts its sensitivity to light according to previous chronic light history, suggesting the existence of a photostasis phenomenon in the human retina as well.

Comparison of photopic negative responses elicited by red and white xenon flashes in monkeys

The photopic negative response (PhNR) is a negative component of the photopic electroretinogram (ERG), and is believed to originate mainly from the retinal ganglion cells. The PhNR is commonly elicited by red light-emitting diodes. The purpose of this study was to compare the amplitude of the PhNR elicited in monkeys by red stimuli and white stimuli obtained from a xenon light source. The PhNRs were elicited from six rhesus monkeys by photopically matched red and white xenon flashes (peak output, 600 nm) on a rod-saturating blue background. The amplitudes of the PhNR elicited by white flashes were compared with those elicited by the red flashes before and after the intravitreal injection of tetrodotoxin (TTX). The differences in PhNR amplitudes between the red and white stimuli, and the changes in the PhNR amplitudes after the injection of TTX, were not statistically significant. These results suggest that red and white xenon flashes are of approximately equal value for assessing inner retinal function using the PhNR under our recording conditions.

Spectral sensitivities of photoreceptors and their role in colour discrimination in the green-backed firecrown hummingbird (Sephanoides sephaniodes)

We studied the photopic spectral sensitivity in the green-backed firecrown, Sephanoides sephaniodes, a South American hummingbird, and its possible ecological relationship with preferred flowers and body colouration. Avian colour vision is in general tetrachromatic with at least four types of cones, which vary in sensitivity from the near ultraviolet (UV) to the red wavelength range. Hummingbirds represent an important family of birds, yet little is known about their eye sensitivity, especially about the role of photoreceptors and their oil droplet complements. The photopic electroretinogram shows a main sensitivity peak at 560 nm and a secondary peak in the UV, and may be explained by the presence of four single cones (lambda max at approximately 370, 440, 508 and 560 nm), and a double cone (lambda max at 560 nm) screened by oil droplets. The flowers preferred by the firecrown are those in which the red-green wavelength region predominates and have higher contrast than other flowers. The crown plumage of males is highly iridescent in the red wavelength range (peak at 650 nm) and UV; when plotted in a high-dimensional tetrachromatic space, it falls in a "red + UV" purple hue line, suggesting a potential significant communication signal for sexual differentiation.

DicerInactivation Leads to Progressive Functional and Structural Degeneration of the Mouse Retina

MicroRNAs (miRNAs) are small, highly conserved molecules that have been shown to regulate the expression of genes by binding to specific target mRNAs. Dicer, an RNase III endonuclease, is essential for the production and function of mature miRNAs, and removal of Dicer has been shown to disrupt many developmental processes. In this study, Dicer was removed specifically from the retina using a floxed Dicer conditional allele and the retinal Chx10Cre transgene. Retinal Dicer knock-out mice displayed a reproducible inability to respond to light. In addition, morphological defects were observed with the formation of photoreceptor rosettes at postnatal day 16, which progressed to more general cellular disorganization and widespread degeneration of retinal cell types as the animals aged. This was accompanied by concomitant decrease in both scotopic and photopic electroretinogram (ERG) responses. Interestingly, removing a single allele of Dicer resulted in ERG deficits throughout life but not to morphological abnormalities. Northern blot analysis of Dicer-depleted retinas showed a decrease in several miRNAs. The observation that progressive retinal degeneration occurred after removal of Dicer raises the possibility that miRNAs are involved in retinal neurodegenerative disorders.

Correlation between Photopic Negative Response and Retinal Nerve Fiber Layer Thickness and Optic Disc Topography in Glaucomatous Eyes

To investigate whether there is a significant correlation between the photopic negative response (PhNR) of the electroretinogram (ERG) and retinal nerve fiber layer thickness and optic disc topography in glaucomatous eyes. Ninety-nine eyes of 53 patients with open-angle glaucoma (OAG) and 30 eyes of 28 normal volunteers were studied. Photopic ERGs were elicited by red stimuli (644 nm, 1600 cd/m(2)) on a blue background (470 nm, 40 cd/m(2)). The mean deviation (MD) of the visual field was obtained by static visual field analyses. The topography of the optic nerve head was determined by confocal scanning laser ophthalmoscopy. The retinal nerve fiber layer thickness (RNFLT) around the optic nerve head was measured with a scanning laser polarimeter. The amplitude of the PhNR and the PhNR/b-wave ratio decreased with an increase in visual field defects. The logarithmic values of the PhNR amplitude and PhNR/b-wave amplitude ratio were significantly correlated with the MD better than the linear values. The PhNR amplitude and PhNR/b-wave amplitude ratio were significantly correlated with the RNFLT and the rim area of the optic disc and with the cup/disc area ratio. These correlations were higher when expressed linearly than when stated logarithmically. The sensitivity and specificity were 77% and 90% for the PhNR amplitude and 70% and 87% for the PhNR/b-wave amplitude ratio when the optimal cutoff values were used. Although the a-wave amplitude correlated with the MD, the a-wave amplitudes of most of the patients fell within the normal range. The correlation between the b-wave amplitude and MD was not significant. The PhNR amplitudes correlate with the decrease in function and morphology of retinal neurons in eyes with OAG. The linear relationship between the PhNR and the structural parameters indicates that inner retinal function declines proportionately with neural loss in eyes with glaucoma.

Changes in retinal thickness are correlated with alterations of electroretinogram in eyes with central retinal artery occlusion

We investigated the relationship between the retinal thickness and electroretinogram (ERG) components in patients with central retinal artery occlusion (CRAO). The optical coherence tomographic (OCT) images and ERGs of the nine patients (six men and three women; mean age, 61.8 years) were retrospectively analyzed. The thickness of the inner and outer retinal layers at 1 and 2 mm nasal and temporal to the fovea was measured in the horizontally scanned OCT images. The ratio of the inner layer thickness/sensory retinal thickness (IT/ST ratio) was calculated. The amplitudes of the a- and b-waves of the mixed rod-cone ERGs and the photopic negative response (PhNR) of the photopic ERGs were analyzed. The ratio of the amplitude of each component in the affected eye to that of the healthy fellow eye (a/f ratio) was calculated. In the chronic phase (1 to 8 months after onset, eight eyes), the inner layer was significantly thinner than that in the acute phase (P = 0.0147, 0.0076, 0.002, and 0.0003 for 2 mm nasal, 1 mm nasal, 1 mm temporal, and 2 mm temporal respectively, within 5 days of onset, six eyes), while the thickness of outer layer was not significantly changed. The ERGs were recorded 6.4 +/- 1.5 days after the onset of CRAO. The median of the a/f ratio was 0.84 in the a-wave, 0.56 in the b-wave, and 0.27 in the PhNR. The IT/ST in the chronic phase was positively correlated with the a/f ratio of the amplitude of the PhNR. Measurement of retinal thickness by OCT can be useful for monitoring the changes following CRAO. The correlation between the retinal thickness, especially inner layer thickness, and the ERG components was determined, suggesting that the PhNR in the acute phase might be a good indicator for predicting the thinning of the damaged retina in the chronic phase.

Photopic Electroretinograms of mGluR6-Deficient Mice

Purpose: To study the properties of the photopic electroretinograms (ERGs) of the metabotropic glutamate receptor subtype 6 (mGluR6)-deficient mice and to investigate the contribution of cone ON-and OFF-pathways to the mouse photopic ERGs. Methods: Photopic ERGs were recorded from mGluR6-deficient and wild-type mice. Photopic ERGs were also recorded after an intravitreous injection ofcis-2,3 piperidine dicarboxylic acid (PDA) to block the transmission of signals from the photoreceptors to the OFF-bipolar cells, horizontal cells, and other inner retinal neurons. Results:The amplitude of the b-wave of the photopic ERG was severely reduced in mGluR6-deficient mice, but a small, slow, positive component was seen after the a-wave. Intravitreous injection of PDA eliminated this positive component. Conclusions: The mGluR6-deficient mouse is a useful animal model to study the contribution of the ON-and OFF-pathways to the mouse ERG.

Photopic ERG Negative Response from Amacrine Cell Signaling in RCS Rat Retinal Degeneration

The authors investigated photopic electroretinographic changes during degeneration in the Royal College of Surgeons (RCS) and transgenic P23H rhodopsin rat models, including the cellular origins of a large corneal-negative component that persists in the RCS rat. Photopic and scotopic electroretinograms (ERGs) were recorded from dystrophic RCS (RCS-p(+)/Lav) rats (4-18 weeks old) and transgenic rhodopsin Pro23His line 1 (P23H) rats (4-30 weeks old). Age-matched congenic (RCS-rdy(+)p(+)/Lav) and Sprague-Dawley rats were used as controls. N-methyl-DL-aspartic acid (NMA), dopamine, and gamma-aminobutyric acid (GABA) were injected intravitreally, and optic nerve sectioning (ONS) was performed to suppress or remove inner retinal neuron activity. Retinal morphology for cone cell counts and immunohistochemistry for quantification of Kir4.1 channels were performed at various stages of degeneration. As degeneration progressed, the photopic ERG of RCS dystrophic rats was distinctly different from that of P23H rats, primarily because of the growth of a corneal-negative response (RCS-NPR) after the b-wave in RCS rats. This response had a peak time similar to the photopic negative response (PhNR) in controls but with a more gradual recovery phase, and it was not affected by ONS. The PhNR in P23H rats declined linearly with the b-wave. NMA and GABA eliminated the RCS-NPR and uncovered a larger b-wave in RCS rats at late stages of degeneration, but NMA had little effect on the ERG in P23H rats. The NMA-sensitive negative response in RCS rats declined with age more slowly than did the NMA-isolated b-wave. The density of Kir4.1 channels at the endfeet of Müller cells and in the proximal retina increased significantly between 6 to 10 weeks and 14 weeks of age in the RCS rat retina but not in the P23H rat retina. The photopic ERG of the dystrophic RCS rat retina becomes increasingly electronegative because of an aberrant negative response, originating from amacrine cell activity, which declines more slowly than the b-wave with degeneration. The absence of this response in the P23H rat indicates that the inner retinal cone pathway pathology is different in the two models. A relative increase in Kir4.1 channels on Müller cells of RCS retina may contribute to the enhanced negative ERG response in the RCS rat.

Intraocular CNTF Reduces Vision in Normal Rats in a Dose-Dependent Manner

CNTF is a neuroprotective agent for retinal degenerations that can cause reduced electroretinogram (ERG) amplitudes. The goal of the present study was to determine the effects of intraocular delivery of CNTF on normal rat visual function. Full-field scotopic and photopic ERG amplitudes and spatial frequency thresholds of the optokinetic response (OKR) of adult Long-Evans rats were measured before and after intravitreous injection of CNTF or subretinal delivery of adenoassociated virus-vectored CNTF (AAV-CNTF) into one eye. Visual acuity was also measured by using the Visual Water Task in AAV-CNTF-injected animals. Multiunit luminance thresholds were recorded in the superior colliculus after CNTF injection, and the eyes were examined histologically. In eyes injected with a high dose of CNTF, ERG amplitudes and OKR thresholds measured through CNTF-injected eyes were decreased by 45% to 70% within 6 days after injection. ERG amplitudes had begun to recover by 21 days, whereas OKR thresholds only began to recover after 56 days. Neither OKR thresholds nor ERG amplitudes fully recovered until 90 to 100 days. When measured in the superior colliculus at 2 weeks after CNTF injection, luminance thresholds were elevated by 0.35 log units. In AAV-CNTF-injected eyes, OKR thresholds, and visual acuity were reduced by approximately 50% for at least 6 months, and scotopic and photopic ERG b-waves were reduced by 30% to 50%. Photoreceptor loss occurred in the injected regions in some of the eyes. By contrast, comparison of dose-response analysis with a dose-response study of light damage strongly suggests that therapeutic doses of CNTF exist that do not suppress ERG responses. Intraocular delivery of CNTF, which preserves photoreceptors in animal models of retinal degeneration, impairs visual function in normal rats at very high doses, but not at lower doses that still provide protection from constant light damage.

Structural and functional maturation of the retina of the albino Hartley guinea pig

Altricial animals, such as rats and mice, are born with their eyes closed, compared to precocial animals, such as guinea pigs and humans, which have their eyes opened at birth. The purpose of this study was to investigate if the retina of guinea pigs (precocial animal) is subjected to a postnatal maturation process similar to that previously reported for rodents. Photopic and scotopic electroretinograms (ERG) and retinal histology were obtained from albino guinea pigs aged P1 to P75. Photopic ERG responses reached maximal amplitudes at P5 (a-and b-waves), that is 5 days (b-wave) to 10 days (a-wave) earlier than scotopic responses. However, the postnatal gain in b-wave amplitude was significantly (P < 0.05) more important for the cone (73.38 +/- 4.4%) signal than for the rod (15.23 +/- 3.96%), suggesting that the rod function is more mature at birth. Similarly, the short latency photopic oscillatory potential (ie: OP2) reached its maximal value 5 days (P10) earlier than its scotopic equivalent (P15), while the long latency OPs (ie: OP3, OP4), reached their maximal values nearly 20 days sooner in scotopic condition. Finally retinal histology revealed a thinning of the retina with age, the latter being most pronounced at the level of the ganglion cell layer (GCL). Our results thus confirm that despite its relative maturity at birth (compared to rodents), the retina of newborn albino guinea pigs undergoes significant postnatal maturation modifying its structure as well as its function, albeit not as extensive as that previously documented for altricial animals.

Photopic ON- and OFF-responses in complete type of congenital stationary night blindness in relation to stimulus intensity

The complete type of congenital stationary night blindness (complete CSNB) is a retinal disorder where the ON-response b-wave of the photopic electroretinogram is reduced, while the ON-response a-wave and OFF-response d-wave are preserved. These findings are related to ON-bipolar cell dysfunction, whereas the effects of myopia, which is usually associated with complete CSNB, have not been studied yet. The aim was to investigate ON-bipolar cell dysfunction in complete CSNB with variable-intensity stimuli, while excluding effects of myopia. ON- and OFF-responses were recorded from six complete CSNB patients, 10 control subjects (no refractive error; emmetropic control group) and 14 myopic subjects with similar refractive error and axial length as those with complete CSNB (myopic control group). Responses were elicited with stimulus intensities from 0.4 to 2.1 log cd s/m2 on a 20 cd/m2 background. Stimulus/response (S/R) functions were fitted to the Naka-Rushton equation and statistically evaluated. In complete CSNB, the S/R function of the a-wave measured at the time corresponding to the controls showed a lower Vmax than for the emmetropic controls, while all parameters were similar to the myopic control group. The b- and d-wave S/R functions of the complete CSNB group were similarly different to both control groups--for the b-wave, the Vmax and n were significantly lower, and for the d-wave, the sigma was significantly higher. These findings suggest that in complete CSNB, dysfunction of ON-bipolar cells influences the dynamics of the ON-response b-wave and OFF-response d-wave, independently of the effects of myopia.

NovelTULP1Mutation Causing Leber Congenital Amaurosis or Early Onset Retinal Degeneration

To report a large, consanguineous Algerian family affected with Leber congenital amaurosis (LCA) or early-onset retinal degeneration (EORD). All accessible family members underwent a complete ophthalmic examination, and blood was obtained for DNA extraction. Homozygosity mapping was performed with markers flanking 12 loci associated with LCA. The 15 exons of TULP1 were sequenced. Seven of 30 examined family members were affected, including five with EORD and two with LCA. All patients had nystagmus, hemeralopia, mild myopia, and low visual acuity without photophobia. Fundus features were variable among EORD patients: typical spicular retinitis pigmentosa or clumped pigmented retinopathy with age-dependent macular involvement. A salt-and-pepper retinopathy with midperipheral retinal pigment epithelium (RPE) atrophy was present in the older patients with LCA, whereas the retina appeared virtually normal in the younger ones. Both scotopic and photopic electroretinograms were nondetectable. Fundus imaging revealed a perifoveal ring of increased fundus autofluorescence (FAF) in the proband, and optical coherence tomography disclosed a thinned retina, mainly due to photoreceptor loss. Linkage analysis identified a region of homozygosity on chromosome 6, region p21.3, and mutation screening revealed a novel 6-base in-frame duplication, in the TULP1 gene. Mutation in the TULP1 gene is a rare cause of LCA/EORD, with only 14 mutations reported so far. The observed intrafamilial phenotypic variability could be attributed to disease progression or possibly modifier alleles. This study provides the first description of FAF and quantitative reflectivity profiles in TULP1-related retinopathy.