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Purpose: Our aim was to compare the electroretinographic (ERG) responses of two eyes obtained by consecutive unilateral recordings to those obtained by a simultaneous bilateral recording in sheep., Methods: Eight sheep underwent two full-field ERG recordings, using two recording strategies of the standard ISCEV protocol: consecutive unilateral recordings of one eye after the other, and simultaneous bilateral recording of both eyes. The order of recording strategy within an animal (unilateral/bilateral), eye recording sequence in the unilateral session (OD/OS), and amplifier channel assignment for each eye were all randomized. To test whether duration of dark adaptation and/or anesthesia affect the results, the ISCEV protocol was recorded bilaterally in six additional eyes following 38 min of patched dark adaptation, as was done for the second eye recorded in the consecutive unilateral recordings., Results: The second recorded eye in the unilateral session had significantly higher scotopic b-wave amplitudes compared to the first recorded eye and to the bilaterally recorded eyes. A-wave amplitudes of the dark-adapted mixed rod-cone responses to a high-intensity flash were also significantly higher in the second eye compared to the first eye recorded unilaterally and to the bilaterally recorded eyes. Light-adapted responses were unaffected by the recording strategy. When the ISCEV protocol was recorded after 38 min of dark adaptation, the scotopic responses were higher than in the first eyes, and similar to those of the second eyes recorded unilaterally, suggesting that indeed the longer duration of anesthesia and dark adaptation are responsible for the increased scotopic responses of the second eye., Conclusions: Consecutive unilateral ERG recordings of two eyes result in higher amplitudes of the dark-adapted responses of the eye recorded second, compared to the eye recorded first and to bilaterally recorded eyes. The differences in scotopic responses can be attributed to different duration of dark adaptation and/or anesthesia of the two consecutively recorded eyes. Photopic responses are not affected. Therefore, simultaneous bilateral ERG responses should be recorded when possible, especially for evaluation of scotopic responses.

Purpose: To determine whether pre-operative electroretinography (ERG) predicts postoperative vision in dogs undergoing retinal reattachment surgery (RRS)., Methods: This 18-month prospective study recorded signalment, duration, cause, and extent of retinal detachment and pre-operative vision status. Rod and mixed rod-cone ERG responses were recorded prior to RRS. Referring veterinary ophthalmologists assessed vision 2 months postoperatively., Results: Thirty dogs (40 affected eyes) aged 4 months to 12.1 years were included. The detachment extent was 150 ° -320 ° in 15 of 40 eyes, 360 ° in 24 of 40 eyes, and not recorded in one eye. Most dogs had a genetic predisposition for retinal detachment. Eight eyes of seven dogs had previous cataract surgery. Mean estimated duration of detachment prior to surgery was 24.5 ± 19.6 days. Pre-operatively, 34 of 40 eyes were blind, two of 40 eyes were sighted, and four of 40 eyes had severely diminished vision. Compared to normative ERG values in our clinics, pre-operative ERGs were classified as "normal" in five of 40 eyes, "attenuated" in seven of 40 eyes, and "flat" in 28 of 40 eyes. Following RRS, the retina was fully reattached in all operated eyes. Two-month postoperatively, 30 of 40 eyes had "normal" vision as defined by referring veterinary ophthalmologists, six of 40 eyes had "limited" or "diminished" vision and four of 40 eyes were blind. Normal vision was regained in 12 of 12 (100%) of eyes with normal or attenuated pre-operative ERG's, but only in 18 of 28 (64%) of eyes with flat pre-operative ERG 's (Linear-by-linear test, P = 0.029)., Conclusions: A recordable pre-operative ERG, even if attenuated, is associated with return of vision in canine RRS patients, and is a favorable prognostic indicator., (© 2017 American College of Veterinary Ophthalmologists.)

Objective: To perform a clinical, ophthalmological, and electroretinographic assessment of retinopathic lesions in German Shepherd dogs., Animals: The study was conducted on 14 German Shepherds diagnosed with retinopathy during the course of an ophthalmological checkup. The animals were systemically healthy police dogs used for patrolling and tracking duties and which were, at times, exposed to considerable physical strain and stress., Procedure: Periodic ophthalmological examinations using slit-lamp biomicroscopy, direct and indirect ophthalmoscopy, and photography, as well as maze testing, were performed on all dogs. Electroretinography (ERG) was performed on 10 affected German Shepherds and eight control dogs., Results: Ophthalmological examination revealed areas of tapetal hyper-reflectivity with pigmented centers, which were characteristic of inactive chorioretinitis. Most of the lesions were in proximity to blood vessels, and in a number of eyes, progression was observed during repeated examinations. Transition from active to inactive lesions, as well as onset in previously unaffected eyes, was also recorded. The ERG recordings showed impaired cone function, with significantly lower b-wave amplitudes and prolonged implicit times, in the mixed rod-cone, photopic, and flicker tests of affected dogs (P < 0.05)., Conclusions: Retinopathy observed in German Shepherd dogs is characterized by areas of tapetal hyper-reflectivity with pigmented centers. The underlying causes of retinopathy in German Shepherd dogs remain unknown, although husbandry conditions and proximity of the lesions to blood vessels may suggest an association with physical exertion or circulatory disorders, respectively., (© 2012 American College of Veterinary Ophthalmologists.)

The full-field, flash electroretinogram (ERG) is now a widely used test of canine retinal function for the clinical diagnosis of hereditary retinal dystrophies and other causes of retinal degeneration, assessment of retinal function in patients with opaque media, ruling out of generalized retinal diseases in patients with sudden loss of vision and in ophthalmological research, as well as in pharmaceutical and toxicological screening for deleterious side effects of drugs and other chemical compounds. In 2002, the first guidelines for clinical ERGs in this species adopted by the European College of Veterinary Ophthalmologists were published. This work provides an update of these guidelines.

Objective: To quantitatively and qualitatively compare electroretinography (ERG) recordings in awake, sedated, and anesthetized dogs., Animals: Six 6-month-old Beagles., Procedures: A brief ERG protocol for dogs was used. Following 1-minute and subsequent 5-minute dark adaptation, mixed rod-cone responses were recorded bilaterally with a handheld multispecies ERG device with dogs in each of 3 states of consciousness: awake, sedated (dexmedetomidine and butorphanol), and anesthetized (atropine and hydromorphone, followed by propofol and midazolam and anesthetic maintenance with isoflurane). Low- and high-frequency noise levels were quantified via Fourier analysis, and the effect of consciousness state on signal amplitude, implicit time, and noise was analyzed via repeated-measures ANOVA. In addition, 13 veterinary ophthalmologists who were unaware of the dogs' consciousness states subjectively graded the ERG recording quality, and scores for each tracing were compared., Results: ERG amplitudes were highest in awake dogs and lowest in anesthetized dogs. Implicit times were shortest in awake dogs and longest in anesthetized dogs. Differences in b-wave amplitudes and a-wave implicit times were significant. Neither low- nor high-frequency noise levels differed significantly among consciousness states. Furthermore, no significant differences were identified among observers' scores assigned to ERG tracings., Conclusions and Clinical Relevance: Anesthesia and sedation resulted in significant attenuation and delay of ERG responses in dogs. Chemical restraint of dogs had no consistently significant effect on low- or high-frequency noise levels or on observer perception of signal quality.

The vertebrate retina, which is part of the central nervous system, is a window into the brain. The present study investigated the extent to which the retina can be used as a model for studying the pathological effects of apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD). Immunohistochemical studies of retinas from young (4 months old) apoE4-targeted replacement mice and from corresponding mice which express the AD benign apoE3 allele, revealed that the density of the perikarya of the different classes of retinal neurons was not affected by apoE4. In contrast, the synaptic density of the retinal synaptic layers, which was assessed immunohistochemically and by immunoblot experiments, was significantly lower in the apoE4 than in the apoE3 mice. This was associated with reduced levels of the presynaptic vesicular glutamatergic transporter, VGluT1, but not of either the GABAergic vesicular transporter, VGaT, or the cholinergic vesicular transporter, VAChT, suggesting that the glutamatergic nerve terminals are preferentially affected by apoE4. In contrast, the post synaptic scaffold proteins PSD-95 and Gephyrin, which reside in excitatory and inhibitory synapses, respectively, were both elevated, and their ratio was not affected by apoE4. Electroretinogram (ERG) recordings revealed significant attenuation of mixed rod-cone responses in dark-adapted eyes of apoE4 mice. These findings suggest that the reduced ERG response in the apoE4 mice may be related to the observed decrease in the retinal nerve terminals and that the retina could be used as a novel model for non-invasive monitoring of the effects of apoE4 on the CNS.

Purpose: Age-related changes in retinal ganglion cell (RGC) activity may impact results of long-term functional studies of disease progression and drug efficacy in humans and animal models. Though these changes can be evaluated using the pattern electroretinogram (PERG), longitudinal studies suffer from failure of follow-up from birth to senescence. Our aim was to perform a long-term, longitudinal study evaluating age-related changes in the rat PERG, by conducting repeated, serial recordings in the same animals. Additionally, we tested the hypothesis that neuroprotective treatment using glatiramer acetate (COP-1) immunization may delay age-related decline in function., Methods: PERG was recorded from six untreated and seven Cop-1-immunized Lewis rats. Recordings were conducted at 2- to 4-week intervals from age 5 to 59 weeks., Results: PERG amplitudes significantly increased between 5 to 7 weeks of age, and decreased from age 30 weeks onward (P = 0.016 and 0.0002, respectively). Amplitudes fluctuated insignificantly in weeks 7 to 30, with peak amplitudes reached at age 18 weeks in most spatial frequencies tested. N2 implicit times were shortened, mainly during weeks 5 to 18 and 40 to 59 (P < 0.001). PERG amplitudes of Cop-1-treated rats were similar to controls (P = 0.137) but peaked later (22-26 weeks)., Conclusions: This 14-month-long study provided accurate measurement of developmental and aging changes of rat RGC function using repeated testing of individual animals. We found functional development to extend beyond the reported period of structural changes. Cop-1-immunized rats were not protected against age-related decline in inner retinal function, although their PERG maturation dynamics were altered.

Objective: Neuroaxonal dystrophy (NAD) is a disease characterized by the sudden onset of neurologic signs in horses ranging from 4 to 36 months of age. Equine degenerative myeloencephalopathy (EDM), a disease that has been associated with low vitamin E concentrations, is considered a more advanced form of NAD. The objective of this report is to describe the electrophysiological features of NAD/EDM in American Quarter horses (QHs). HORSES: Six NAD/EDM-affected QHs and six unaffected QHs were evaluated by ophthalmic examination and electroretinography. Five of the NAD/EDM-affected QH and five unaffected QHs were also evaluated by electroencephalography (EEG)., Results: Ophthalmic examination, ERGs, and EEGs were unremarkable in NAD/EDM cases., Conclusions: Neuroaxonal dystrophy/EDM does not appear to cause clinical signs of ocular disease or functional ERG/EEG deficits in QHs., (© 2012 American College of Veterinary Ophthalmologists.)

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.

These procedures described for the dog ERG were approved at the 1st European Conference on Veterinary Visual Electrophysiology in Vienna, Austria, May 30, 2000. Dr. Narfström was Chair of the Committee for a Harmonized ERG Protocol, appointed by the European College of Veterinary Ophthalmology (ECVO), and Dr. Ofri was secretary. The other coauthors are committee members. Guidelines for ERG procedures in other animal species for clinical and laboratory studies are planned for in the future and the present guidelines are planned to be revised on a biannual basis. A brief report of the recommended procedures is available in the Conference Proceedings book.

Electroretinogram (ERG) and visual-evoked potentials (VEPs) are used in veterinary ophthalmology to assess the functional integrity of the retina and the central visual pathway. The interpretation of altered electrophysiologic potentials in diseases can be of great diagnostic value, although it is important to be aware of technical factors and the limitations of these techniques which may result in over-interpretation and misinterpretation of the recordings, such that they are similar to those found in disease-related electrophysiologic changes. The recorded potentials represent the differences in voltage between the active and reference electrodes. The ground electrode serves as zero. A differential or instrumentation amplifier selectively amplifies signals of interest while rejecting noise. Differences between inputs are amplified, whereas common signals are rejected in a process called common mode rejection (CMR). In order for CMR to be most effective in reducing noise, the electrode impedances should be balanced. Filters are part of the differential amplifier as they remove unwanted noise of a certain frequency. The frequency bandwidth, or passband, is the range of frequencies between low- and high-frequency filter settings that are not filtered out. Major sources of noise that cause interpretation artifacts are power lines, amplifier noise, physiologic activity, electrochemical electrode noise and circular grounds. Noise reduction is achieved with high amplifier input impedance, balanced electrode impedances, CMR, filters and signal averaging. Maintaining electrodes in good condition, achieving proper contact between electrode and animal, and keeping electrode leads short aid in achieving noise reduction.

Objective: Electroretinography (ERG) is used prior to cataract removal surgery to assess retinal function. We aimed to replicate and improve upon previous studies by performing a full ECVO protocol and by examining the retina post‐surgery in all patients. Animals studied: One hundred twenty‐seven eyes from 67 dogs were included in the study. Procedures: A full ECVO protocol electroretinography, which includes extensive rod and cone analysis, was performed on all dogs presenting for cataract surgery. Results: Our main findings were that amplitudes, but not implicit times of rod responses decreased with advanced cataracts. Amplitudes of the single flash rod and rod flicker responses were significantly lower in eyes with mature cataracts, and the former also decreased in hypermature cataracts. Cone flicker amplitude responses were also significantly lower in eyes with mature and hypermature cataracts. However, mixed single flash rod‐cone and cone responses, with the exception of the mixed rod‐cone a‐wave amplitude in eyes with hypermature cataracts, were unaffected by cataract stage. The b‐wave amplitude of the scotopic, mixed rod‐cone, and photopic cone responses were affected by age and decreased by an average of 2.9, 7.5, and 1.5 μV/year, retrospectively (p < 0.01). Conclusions: Lower ERG amplitudes in canine cataract patients may result from aging or the presence of advanced cataracts and may not indicate the presence of retinal disease. [ABSTRACT FROM AUTHOR]

Purpose: To establish whether there is cone contribution to retinal function and structure in chinchillas (Chinchilla lanigera), in view of the prevailing notion that this species possesses a pure rod retina. Methods: Photopic electroretinography (ERG) responses to high‐intensity flashes (10 and 25 cd*s/m2) were recorded unilaterally in six pigmented chinchillas following 10 minutes of light adaptation (30 cd/m2). Retinas of two animals were studied histologically, and immunohistochemistry (IHC) was conducted to detect the presence of short and medium/long wavelength cone photoreceptors. Results: ERG recordings revealed photopic responses, albeit of low amplitudes. Histopathology demonstrated presumptive cone inner segments in the photoreceptor layer. Presence of cone photoreceptors was confirmed by IHC. Cone density was higher in the central retina, and red/green cones outnumbered blue cones. Conclusions: Our results provide convincing evidence for the presence of functioning cone photoreceptors in the chinchilla retina, disproving the established belief that the species has a pure rod retina. [ABSTRACT FROM AUTHOR]

Achromatopsia causes severely reduced visual acuity, photoaversion, and inability to discern colors due to cone photoreceptor dysfunction. In 2010, we reported on day-blindness in sheep caused by a stop-codon mutation of the ovine CNGA3 gene and began gene augmentation therapy trials in this naturally occurring large animal model of CNGA3 achromatopsia. The purpose of this study was to evaluate long-term efficacy and safety results of treatment, findings that hold great relevance for clinical trials that started recently in CNGA3 achromatopsia patients. Nine day-blind sheep were available for long-term follow up. The right eye of each sheep was treated with a single subretinal injection of an Adeno-Associated Virus Type 5 (AAV5) vector carrying either a mouse (n = 4) or a human (n = 5) CNGA3 transgene under control of the 2.1-Kb red/green opsin promoter. The efficacy of treatment was assessed periodically with photopic maze tests and electroretinographic (ERG) recordings for as long as 74 months postoperatively. Safety was assessed by repeated ophthalmic examinations and scotopic ERG recordings. The retinas of three animals that died of unrelated causes >5 years post-treatment were studied histologically and immunohistochemically using anti-hCNGA3 and anti-red/green cone opsin antibodies. Passage time and number of collisions of treated sheep in the photopic maze test were significantly lower at all follow-up examinations as compared with pretreatment values (p = 0.0025 and p < 0.001, respectively). ERG Critical Flicker Fusion Frequency and flicker amplitudes at 30 and 40 Hz showed significant improvement following treatment (p < 0.0001) throughout the study. Ophthalmic examinations and rod ERG recordings showed no abnormalities in the treated eyes. Immunohistochemistry revealed the presence of CNGA3 protein in red/green opsin-positive cells (cones) of the treated eyes. Our results show significant, long-term improvement in cone function, demonstrating a robust rescue effect up to six years following a single treatment with a viral vector that provides episomal delivery of the transgene. This unique follow-up duration confirms the safe and stable nature of AAV5 gene therapy in the ovine achromatopsia model. [ABSTRACT FROM AUTHOR]

Objective: To study retinal morphology and function in the collared peccary, an ungulate species distantly related to the domestic pig. Animal studies: Twenty captive peccaries anesthetized for routine health examinations. Procedures No abnormalities were noted on a complete ophthalmic examination. Fundi were examined ophthalmoscopically and photographed. The eyes of an individual that died of unrelated, nonocular reasons were studied histologically and by immunohistochemistry. Scotopic, mixed rod–cone, and photopic electroretinography (ERG) responses were recorded using the 'QuickRetCheck' (n = 6) and 'Dog diagnostic' (n = 5) protocols of the Handheld Multispecies ERG (HMsERG). Results: The fundus of the peccary is atapetal, with varying amounts of pigmentation seen ophthalmoscopically, and histologically in the retinal pigment epithelium (RPE) and choroid. The retina is holangiotic with dichotomously branching vessels. These cross, and apparently loop on, the optic disk surface, but no venous circle was seen. Immunohistochemistry suggests a high concentration of cone photoreceptors with red/green cones being more abundant than blue cones. Rod ERG responses were very low with no evident dark adaptation. Mixed rod–cone and cone ERG response amplitudes were low compared to those of domestic pigs, but quite similar to those of minipigs. Conclusions: To the best of our knowledge, this study describes the collared peccary's retinal features for the first time. A comparison of our findings with data from other ungulate species shows some similarities between the peccary and pig retinas. Further studies are warranted to determine whether the peccary can be used alongside the pig as an animal model in retinal studies. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate an innovative approach for closing retinal tears using DuraSeal™ (DS) hydrogel sealant in a rabbit model.Methods: Retinal detachment with a small tear was performed on 20 New Zealand rabbits. Thereafter, rabbits were divided into two groups; the experimental group received a transscleral injection of 0.1 ml DS into the subretinal space whereas the control group received sham injection of saline. Eyes were clinically evaluated using indirect ophthalmoscopy, retinal function was recorded in ten rabbits by electroretinography and the sealant's toxicity was evaluated histopathologically.Results: We found that the DS hydrogel was easily injected transsclerally into the subretinal space of the detached retinas with no major complications. Retinal reattachment was seen in both groups within 2 weeks with no toxicity to the sensory retina. There were no significant differences in retinal function between groups.Conclusion: Subretinal injection of hydrogel through a transscleral route is easy to perform and may open a new avenue in the treatment of retinal detachment. However, the efficacy of the DS as a tamponade for sealing retinal tear is yet to be definite. Long-term clinical, functional, and toxicological studies are needed to evaluate its full potential for clinical applications. [ABSTRACT FROM AUTHOR]

Purpose: Retinal ischemia is a common cause of visual impairment and blindness. Sildenafil, a PDE5 inhibitor which inhibits cGMP degradation and in turn prolongs the effect of nitric oxide, has been shown to be protective in a number of ischemia/reperfusion (I/R) injuries, as well as in neuronal damage. We hypothesized that treatment with sildenafil might be neuroprotective in a model of acute retinal I/R injury. Methods: Anterior chamber cannulation was performed to induce unilateral I/R injury in 38 Lewis rats. Animals received intraperitoneal injections of sildenafil (0.5 and 1 mg/kg once a day, for a period of 7 and 18 days, respectively), or saline. Electroretinography recordings, retinal ganglion cell (RGC) counts following retrograde labeling with fluorogold, histopathology, and immunohistochemistry (IHC) using antibodies against PDE5, NOS2, caspase-3, caspase-9, and Bcl-2 were conducted. Results: No significant differences in electroretinography, RGC counts, or retinal morphometry were observed between experimental eyes of sildenafil- and saline-treated animals. A tendency toward less necrosis in histopathology, and a slight trend toward lower PDE5, NOS2, and caspase-9 and higher Bcl-2 IHC scores were evident in experimental retinas of sildenafil-treated animals. Conclusions: Electroretinography, RGC counts, and retinal morphometry failed to show any neuroprotective effect of sildenafil in acute retinal I/R injury in rats. A slight positive effect of sildenafil was qualitatively indicated by histopathology and IHC. [ABSTRACT FROM AUTHOR]

Purpose To conduct ophthalmic, behavioral, electrophysiological, and genetic testing on two related Gordon setters presented for day blindness and compare findings with those of nine related and unrelated Gordon setters. Methods All dogs underwent comprehensive ophthalmic examination. Maze testing was conducted under different light intensities. Rod and cone function was assessed electroretinographically. DNA samples were screened for five canine retinal disease gene mutations. Results Ophthalmic examination was unremarkable in all dogs. There was no notable difference between day blind dogs and the reference population in scotopic and mesopic maze tests. Day blind dogs performed worse in the photopic maze with slower course completion time and more obstacle collisions. Electroretinography revealed extinguished cone function in day blind dogs and depressed rod responses in all but two reference dogs. One reference population dog presented with day blindness 1 year after initial examination. Mutations that cause achromatopsia (in CNGB3) and cone-rod dystrophies (in ADAM9 and IQCB1) were not detected in any dog tested, although five reference dogs were carriers of the mutation in C2orf71 that causes rod-cone degeneration 4 ( rcd4) in Gordon setters and in polski owczarek nizinny dogs. Conclusions This report describes a novel retinopathy in related Gordon setters that has clinical signs and vision testing results consistent with achromatopsia but electroretinographic results suggestive of cone-rod dystrophy. The majority of Gordon setters in this study had low rod responses on electroretinography but it is unclear whether this was indicative of rod dysfunction or normal for the breed. Longer-term observation of affected individuals is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Though the rat is increasingly used as an animal model in ophthalmic research, including the study of glaucoma, little is known about age-related changes in its inner retinal function. The aim of this study was to evaluate these changes in the rat during the first 18weeks of life. The pattern electroretinogram (PERG) was used to monitor inner retinal activity in 16 developing rats. In each animal, recordings were conducted at ages 3, 5, 7, 11, 14 and 18weeks to assess age-related changes in function. Signals were evoked by five stimuli of progressively increasing check width (subtending 82–1312 arc minutes of visual angle) that were projected directly onto the fundus through a specially modified ophthalmoscope which allowed visual and manual control of stimulus quality. Poor signal:noise ratio prevented signal analysis at age 3weeks. Subsequently, PERG amplitude increased significantly, up to 242% (depending on stimulus check width), during weeks 5–11. After peaking at 11weeks, signal amplitude declined moderately. Signal latency mirrored that of amplitude, decreasing during the first 11weeks, and then increasing steadily. Latency was not affected by stimulus check width. Age was highly correlated with P1 latency (R 2 =0.80) and moderately correlated with N2 latency (R 2 =0.52). Therefore, we propose that studies of inner retinal diseases (such as glaucoma) in the rat model should use age-matched controls, as electrophysiological results may be confounded by age-related changes. The rat PERG undergoes many of the age-related changes that have been reported in humans, and thus may serve as an animal model to study development of inner retinal function. [Copyright &y& Elsevier]

Abstract: Voltage gated sodium channels (Nav), are proposed mediators of neuronal damage in ischemic and excitotoxicity disease models. We evaluated the neuroprotective effects of lamotrigine, a Nav blocker, in the acute and chronic rat ocular hypertension models. Additionally, expression of the main Nav subtypes in the optic nerve (ON) was assessed to test whether their upregulation plays a role in the pathogenesis of ocular hypertension induced optic neuropathy. Unilateral intraocular pressure (IOP) elevation was induced for 60 min (80 mmHg) and 14–21 days (670–859 mmHg*day) in the acute and chronic models, respectively. Lamotrigine was administered at dosages of 10 mg/kg twice daily and 12.5 mg/kg once daily in the acute (n = 9) and chronic (n = 11) trials, respectively. Treatment began 2 days prior to IOP elevation until sacrifice. Outer and inner retinal function was evaluated with dark- and light-adapted flash electroretinography and pattern electroretinography, respectively, 6 and 14 days post acute IOP elevation and 13, 28 and 48 days post chronic IOP elevation. Retinal ganglion cell and axon densities and inflammatory reaction were evaluated through Fluorogold, Bielschowsky's silver impregnation and ED1 labeling respectively. Immunohistochemistry for Nav1.1, 1.2 and 1.6 was performed in ONs of untreated rats 7 and 15 days post IOP elevation in the acute model and after 7, 28 and 50 days in the chronic model. In the acute model, no differences were found in the a-wave amplitudes between lamotrigine-treated and vehicle-treated rats. B-wave amplitudes decreased by 40–66% in both treatment groups 6 days post IOP elevation, with no significant difference between groups (p = 0.38). However, a partial recovery of b-wave amplitudes was found in lamotrigine-treated rats between day 6 and day 14 post procedure (p < 0.05). No differences were found in any other parameter tested in this model. Similarly, lamotrigine treatment did not result in any beneficial effect in structural parameters of the chronic model. Functional evaluation of this model was inconclusive due to super-normal values in the hypertensive eyes. Up-regulation of Nav1.1 and 1.2 expression was found in both models, beginning by day 7; an increase of the former continued in a time-dependent manner in the chronic model. Nav1.6 labeling was inconclusive. In conclusion we found lamotrigine treatment to be mostly ineffective in both acute and chronic ocular hypertension models. [Copyright &y& Elsevier]