Pattern Electroretinogram Response Research Articles

A comprehensive dataset of pattern electroretinograms for ocular electrophysiology research

The Pattern Electroretinogram (PERG) is an essential tool in ophthalmic electrophysiology, providing an objective assessment of the central retinal function. It quantifies the activity of cells in the macula and the ganglion cells of the retina, assisting in the differentiation of macular and optic nerve conditions. In this study, we present the IOBA-PERG dataset, an extensive collection of 1354 transient PERG responses accessible on the PhysioNet repository. These recordings were conducted at the Institute of Applied Ophthalmobiology (IOBA) at University of Valladolid, over an extended period spanning nearly two decades, from 2003 to 2022. The dataset includes 336 records, ensuring at least one PERG signal per eye. The dataset thoughtfully includes demographic and clinical data, comprising information such as age, gender, visual acuity measurements, and expert diagnoses. This comprehensive dataset fills a gap in ocular electrophysiological repositories, enhancing ophthalmology research. Researchers can explore a broad range of eye-related conditions and diseases, leading to enhanced diagnostic accuracy, innovative treatment strategies, methodological advancements, and a deeper understanding of ocular electrophysiology.

Increasing the number and intensity of shock tube generated blast waves leads to earlier retinal ganglion cell dysfunction and regional cell death

The purpose of this study was to examine the effect of a blast exposure generated from a shock tube on retinal ganglion cell (RGC) function and structure. Mice were exposed to one of three blast conditions using a shock tube; a single blast wave of 20 PSI, a single blast wave of 30 PSI, or three blast waves of 30 PSI given on three consecutive days with a one-day inter-blast interval. The structure and function of the retina were analyzed using the pattern electroretinogram (PERG), the optomotor reflex (OMR), and optical coherence tomography (OCT). The in vivo parameters were examined at baseline, and then again 1-week, 4-weeks, and 16-weeks following blast exposure. The number of surviving RGCs was quantified at the end of the study. Analysis of mice receiving a 20 PSI injury showed decreased PERG and OMR responses 16-weeks post blast, without evidence of changed retinal thickness or RGC death. Mice subjected to a 30 PSI injury showed decreased PERG responses 4 weeks and 16 weeks after injury, without changes in the retinal thickness or RGC density. Mice subjected to 30 PSI X 3 blast exposures had PERG deficits 1-week and 4-weeks post exposure. There was also significant change in retinal thickness 1-week and 16-weeks post blast exposure. Mice receiving 30 PSI X 3 blast injuries had regional loss of RGCs in the central retina, but not in the mid-peripheral or peripheral retina. Overall, this study has shown that increasing the number of blast exposures and the intensity leads to earlier functional loss of RGCs. We have also shown regional RGC loss only when using the highest blast intensity and number of blast injuries.

Assessment of the uniform field electroretinogram for mouse retinal ganglion cell functional analysis.

The uniform field electroretinogram (UF-ERG) has been suggested as an alternative to the pattern electroretinogram (PERG) for non-invasive assessment of retinal ganglion cell (RGC) function in primates. We evaluated the validity of the UF-ERG to assess mouse RGC activity in vivo. Unilateral optic nerve crush (ONC) was performed on adult C57BL/6J mice. Contralateral eyes with uncrushed optic nerves and eyes from surgically naive mice served as experimental controls. Electrophysiological visual assessment was performed at 12weeks post-ONC. Flash-mediated visual-evoked cortical potentials (VEPs) were measured to confirm the robustness of the ONC procedure. Full-field flash ERGs were used to interrogate photoreceptor and retinal bipolar cell function. RGC function was assessed with pattern ERGs. Summed onset and offset UF-ERG responses to alternating dark and light uniform field flash stimuli of different intensities and wavelengths were recorded from ONC and control eyes, and relative differences were compared to the PERG results. Following electrophysiological analysis, RGC loss was monitored by immunohistochemical staining of the RGC marker protein, RBPMS, in post-mortem retinal tissues. ONC dramatically impacts RGC integrity and optic nerve function, demonstrated by reduced RGC counts and near complete elimination of VEPs. ONC did not affect scotopic ERG a-wave and b-wave amplitudes, while PERG amplitudes of eyes subjected to ONC were reduced by approximately 50% compared to controls. Summation of ON and OFF UF-ERG responses did not reveal statistically significant differences between ONC and control eyes, regardless of visual stimulus. PERG responses are markedly impaired upon ONC, while UF-ERG responses are not significantly affected by surgical trauma to RGC axons in mice. The more closely related pattern and uniform field ERGs recorded in primates suggests species-specific differences in RGC features or subpopulations corresponding to PERG and UF-ERG response generators, limiting the utility of the UF-ERG for mouse RGC functional analysis.

Replication of Reduced Pattern Electroretinogram Amplitudes in Depression With Improved Recording Parameters.

Background: The retina has gained increasing attention in non-ophthalmological research in recent years. The pattern electroretinogram (PERG), a method to evaluate retinal ganglion cell function, has been used to identify objective correlates of the essentially subjective state of depression. A reduction in the PERG contrast gain was demonstrated in patients with depression compared to healthy controls with normalization after remission. PERG responses are not only modulated by stimulus contrast, but also by check size and stimulation frequency. Therefore, the rationale was to evaluate potentially more feasible procedures for PERG recordings in daily diagnostics in psychiatry.Methods: Twenty-four participants (12 patients with major depression (MDD) and 12 age- and sex-matched healthy controls) were examined in this pilot study. We investigated PERG amplitudes for two steady-state pattern reversal frequencies (12.5/18.75 rps) and four sizes of a checkerboard stimulus (0.8°, 1.6°, 3.2°, and 16°) to optimize the PERG recordings in MDD patients.Results: Smaller PERG amplitudes in MDD patients were observed for all parameters, whereby the extent of the reduction appeared to be stimulus-specific. The most pronounced decline in the PERG of MDD patients was observed at the higher stimulation frequency and the finest pattern, whilst responses for the largest check size were less affected. Following the PERG ratio protocol for early glaucoma, where similar stimulus dependent modulations have been reported, we calculated PERG ratios (0.8°/16°) for all participants. At the higher frequency (18.75 rps), significantly reduced ratios were observed in MDD patients.Conclusion: The “normalization” of the PERG responses—via building a ratio—appears to be a very promising approach with regard to the development of an objective biomarker of the depressive state, facilitating inter-individual assessments of PERG recordings in patients with psychiatric disorders.

Retinal ganglion cell ablation in guinea pigs

Guinea pigs are a common model of human ocular conditions; however, their visual function has not been fully characterized. The purpose of this study was to determine the contributions of retinal ganglion cells to structural and functional measures in guinea pigs. Healthy adult guinea pigs (n = 12) underwent unilateral optic nerve crush. Retinal structure was assessed with spectral domain optical coherence tomography (OCT), and thickness of the ganglion cell/nerve fiber layer (GC/NFL) was determined. Visual function was assessed with optomotor tracking of a drifting grating and light adapted electroretinograms (ERGs). From flash ERGs, a-wave, b-wave, oscillatory potentials (OPs), and photopic negative response (PhNR) were analyzed. From pattern ERGs, N1P1 and P1N2 were analyzed. Histological studies were done at various time points for ganglion cell quantification. Optomotor tracking was absent in optic nerve crush eyes following optic nerve crush. Significant thinning of the GC/NFL was evident four weeks following the crush. Flash ERGs revealed a significant reduction in the OP1 amplitude two weeks following crush (P < 0.01) and in the PhNR amplitude six weeks following crush (P < 0.01). There were no significant changes in a-wave, b-wave, or pattern ERG responses (P > 0.05 for all). In vivo OCT imaging showed progressive thinning of inner retinal layers. Ganglion cell density, quantified histologically, was significantly reduced by 75% in the optic nerve crush eye compared to the control eye at four weeks following crush. These findings indicate that retinal ganglion cells contribute to the PhNR and OP1 components of the full field flash ERG, but not significantly to the pattern ERG in guinea pigs. This study demonstrates that OCT imaging and full field flash ERGs are valuable in assessing retinal ganglion cell loss in vivo in guinea pigs and will help to further establish the guinea pig as a model of human ocular pathologies.

Diabetes exacerbates the early RGCs loss of function in the DBA/2J inherited mouse model of Glaucoma

AbstractPurposeGlaucoma is a multifactorial disease that progressively determines the dysfunction and the subsequent death of retinal ganglion cells (RGCs), depending or not by the intraocular pressure (IOP) elevation. The possible influence of diabetes as a risk and/or exacerbating factor for glaucoma has been postulated, but the relationship between diabetes and glaucoma remains controversial. The purpose of this study is to clarify the effect of diabetes in the early progression of glaucoma during the RGCs dysfunction stage preceding the IOP elevation and the cell death.MethodsDBA/2J glaucomatous mice were injected with streptozotocin (STZ) to obtain a combined model of diabetes and glaucoma. In addition, non‐treated DBA/2J mice and STZ‐injected C57BL/6J were analyzed respectively as glaucomatous and diabetic only controls. RGCs and outer retina activities were evaluated performing respectively pattern electroretinogram (PERG) and flash electroretinogram (FERG) from 4 to 6 month of age. Additionally, IOP and glycaemia were followed up to monitor the progression of the disease.ResultsAs expected, non‐treated DBA/2J mice didn’t show any elevation of IOP nor alteration of FERG response during this time window. However, this group showed an age‐dependent worsening of the amplitude and the latency related to the PERG response. C57BL/6J mice treated with STZ showed an IOP‐independent decrease in PERG response preceding alterations of FERG. Interestingly, hyperglycemia determined the exacerbation of the PERG response in STZ‐treated DBA/2J compared to both diabetic and glaucomatous only groups starting from the very beginning of the diabetic condition independently from both IOP and FERG changings.ConclusionOur results show that diabetes act as an exacerbating factor for the progression of glaucoma. Indeed, hyperglycemic condition act as a further stressor which leads to a quicker loss of RGCs function and cell death.

Adaptation of retinal ganglion cell function during flickering light in the mouse

Rapid dilation of retinal vessels in response to flickering light (functional hyperemia) is a well-known autoregulatory response driven by increased neural activity in the inner retina. Little is known about flicker-induced changes of activity of retinal neurons themselves. We non-invasively investigated flicker-induced changes of retinal ganglion cell (RGC) function in common inbred mouse strains using the pattern electroretinogram (PERG), a sensitive measure of RGC function. Flicker was superimposed on the pattern stimulus at frequencies that did not generate measurable flicker-ERG and alter the PERG response. Transition from flicker at 101 Hz (control) to flicker at 11 Hz (test) at constant mean luminance induced a slow reduction of PERG amplitude to a minimum (39% loss in C57BL/6J mice and 52% loss in DBA/2J mice) 4–5 minutes after 11 Hz flicker onset, followed by a slow recovery to baseline over 20 minutes. Results demonstrate that the magnitude and temporal dynamics of RGC response induced by flicker at 11 Hz can be non-invasively assessed with PERG in the mouse. This allows investigating the functional phenotype of different mouse strains as well as pathological changes in glaucoma and optic nerve disease. The non-contact flicker-PERG method opens the possibility of combined assessment of neural and vascular response dynamics.

Neuroenhancement and neuroprotection by oral solution citicoline in non-arteritic ischemic optic neuropathy as a model of neurodegeneration: A randomized pilot study.

PurposeTo evaluate whether treatment with Citicoline in oral solution (OS-Citicoline) would increase visual function, retinal ganglion cells (RGCs) function, and neural conduction along visual pathways (neuroenhancement), and/or induce preservation of RGCs fibers’ loss (neuroprotection) in non-arteritic ischemic optic neuropathy (NAION), a human model of neurodegeneration.MethodsThirty-six patients with NAION and 20 age-matched controls were enrolled. Nineteen NAION patients received 500 mg/day of OS-Citicoline for a 6-month period followed by 3-month of wash-out (NC Group); 17 NAION patients were not treated (NN Group) from baseline to 9 months. In all subjects at baseline, and in NC and NN eyes at 6 and 9 months of follow-up, we assessed Visual Acuity (VA), Pattern Electroretinogram (PERG), Visual Evoked Potentials (VEP), retinal nerve fiber layer thickness (RNFL-T), and Humphrey 24–2 visual field mean deviation (HFA MD). Mean differences were statistically evaluated with ANOVA between Groups, and linear correlations were analysed with Pearson’s test.ResultsAt 6 months, significant differences between groups for all parameters were observed (ANOVA, p<0.01). In NC eyes, VA increased, PERG responses increased, VEP recordings improved and were significantly correlated with increases in HFA MD (p<0.01), and RNFL-T was unmodified or improved. In contrast, in NN eyes, VA, PERG, VEP responses, RNFL-T, and HFA MD were further worsened. Significant differences were still present at 9-month follow-up in the NN Group and after 3 months of OS-Citicoline wash-out in NC eyes.ConclusionsOS-Citicoline treatment induced neuroenhancement (improvement in RGCs function and neural conduction along visual pathways related to improvement of visual field defects) and neuroprotection (unmodified or improved RNFL morphological condition) in a human model of NAION involving fast RGCs degeneration.Trial registrationClinicalTrials.gov NCT03758118.

Blast-Mediated Traumatic Brain Injury Exacerbates Retinal Damage and Amyloidosis in the APPswePSENd19e Mouse Model of Alzheimer's Disease.

PurposeTraumatic brain injury (TBI) is a risk factor for developing chronic neurodegenerative conditions including Alzheimer's disease (AD). The purpose of this study was to examine chronic effects of blast TBI on retinal ganglion cells (RGC), optic nerve, and brain amyloid load in a mouse model of AD amyloidosis.MethodsTransgenic (TG) double-mutant APPswePSENd19e (APP/PS1) mice and nontransgenic (Non-TG) littermates were exposed to a single blast TBI (20 psi) at age 2 to 3 months. RGC cell structure and function was evaluated 2 months later (average age at endpoint = 4.5 months) using pattern electroretinogram (PERG), optical coherence tomography (OCT), and the chromatic pupil light reflex (cPLR), followed by histologic analysis of retina, optic nerve, and brain amyloid pathology.ResultsAPP/PS1 mice exposed to blast TBI (TG-Blast) had significantly lower PERG and cPLR responses 2 months after injury compared to preblast values and compared to sham groups of APP/PS1 (TG-Sham) and nontransgenic (Non-TG-Sham) mice as well as nontransgenic blast-exposed mice (Non-TG-Blast). The TG-Blast group also had significantly thinner RGC complex and more optic nerve damage compared to all groups. No amyloid-β (Aβ) deposits were detected in retinas of APP/PS1 mice; however, increased amyloid precursor protein (APP)/Aβ-immunoreactivity was seen in TG-Blast compared to TG-Sham mice, particularly near blood vessels. TG-Blast and TG-Sham groups exhibited high variability in pathology severity, with a strong, but not statistically significant, trend for greater cerebral cortical Aβ plaque load in the TG-Blast compared to TG-Sham group.ConclusionsWhen combined with a genetic susceptibility for developing amyloidosis of AD, blast TBI exposure leads to earlier RGC and optic nerve damage associated with modest but detectable increase in cerebral cortical Aβ pathology. These findings suggest that genetic risk factors for AD may increase the sensitivity of the retina to blast-mediated damage.

Decoding PERG: A neuro-ophthalmic retinal ganglion cell function review.

Currently, the clinical evaluation of neuro-ophthalmologic diseases are mainly focused on identifying stages where structural or functional damage occur. Recognition of retinal ganglion cell (RGC) functional patterns as well as monitoring RGC dysfunction can be performed using steady-state pattern electroretinogram (PERG). The analysis of the amplitude and latency shift aid on providing information on early damage or monitoring of the RGC, allowing for prompt clinical intervention and management modification, potentially changing the natural history of the disease. The purpose of this article is to review the latest findings in PERG, in early manifest glaucoma, non arteritic ischemic optic neuropathy, multiple sclerosis with unilateral recovered optic neuritis and its fellow eyes. The steady-state PERG responses provide new and early specific information in neuro-ophthalmic diseases affecting the inner retina. Steady state PERG presents specific amplitude and latency outcomes based on the neuro-ophthalmic disease affecting the inner retina, allowing early recognition of changes at the level of RGC and the degree of RGC dysfunction. In addition, PERG alterations may be induced in healthy subjects as well as susceptible eyes using different stress tests such as head down tilting or water drinking tests.

Analysis of pattern electroretinogram signals of early primary open-angle glaucoma in discrete wavelet transform coefficients domain.

To evaluate discrete wavelet transform coefficients and identify descriptors of pattern electroretinogram (PERG) waveforms in order to determine PERG characteristics for optimizing the diagnosis of early primary open-angle glaucoma (POAG). Pattern electroretinogram was performed in 30 normal eyes and 30 eyes with primary open-angle glaucoma according to the ISCEV protocol. The check size was 0.8° and 16°, and the color was black/white in both groups. The results were analyzed in time domain (TD) and discrete wavelet transform (DWT) using the MATLAB software. The mean value, standard deviation, and relative energy of level 6 and 7 detail coefficients (d6, d7) and level 7 approximation coefficients (a7) of Daubechies 4 (db4), Daubechies 8 (db8), Symlet 5 (sym5), Symlet 7 (sym7), and Coiflet 5 (coif5) wavelets were calculated. In all the mentioned wavelets, DWT descriptors were extracted. Signals were reconstructed by inverse DWT. All data obtained by TD and DWT analyses were compared between the two groups. In both check sizes, a significant attenuation of N95 amplitude was seen in the patient group. The relative energy of a7 of db8 increased significantly in the POAG group in the 0.8° check size. In larger check stimuli, the relative energy of d7 of coif5 decreased significantly and the standard deviation of d7 of sym7 increased markedly in glaucomatous patients (P < 0.05). In small stimuli, N95 descriptor (7N) of db8 had the highest value and showed a significant increase as compared to the POAG group. In the 16° check size, there was no significant difference. A strong correlation was seen between reconstructed signals and originals (r = 0.99). The DWT can quantify PERG responses more accurately. In agreement with TD and wavelet coefficients domain results, 7N of db8 decomposition can be used as a good indicator for early detection of POAG.

Macular and Multifocal PERG and FD-OCT in Preperimetric and Hemifield Loss Glaucoma.

To evaluate the ability of macular and multifocal (mf) pattern electroretinogram (PERG) to differentiate preperimetric glaucoma (PG) and glaucoma with hemifield loss (GHL) from controls, to compare the discrimination ability of PERG and fourier-domain optical coherence tomography (FD-OCT), and to assess the relationship between measurements. Standard automated perimetry, steady-state and transient PERG and mfPERG measurements were obtained from PG (n=14, 24 eyes), GHL (n=5, 7 eyes), and controls (n=19, 22 eyes). Circumpapillary retinal nerve fiber layer (cpRNFL), full-thickness macula, and segmented macular layer thicknesses on FD-OCT were investigated. Measurements were compared using mixed effects linear models. The relationships between measurements and the diagnostic performance of each technology were assessed. Compared with controls, average P50 peak time transient PERG responses were reduced in PG and GHL, whereas average latency and amplitude steady-state and mfPERG responses were abnormal only in GHL. cpRNFL and macular thickness measurements in PG and GHL differed significantly from controls. A significant relationship was found between PERG and most FD-OCT or SAP parameters. Partial least squares discriminant analysis revealed that OCT parameters, along with mfPERG and transient PERG parameters had similar ability to discriminate PG and GHL from healthy controls. PERG and OCT parameters may be abnormal, with significant correlations between measurements, in PG eyes. Both technologies may be useful for detection of early glaucoma.

The neuro-ophthalmological effects related to long-term occupational exposure to organic solvents in painters.

Organic solvents are widely used in many industries, and usually, exposure occurs with mixtures of solvents. Organic solvent mixtures are known for their ability to affect tissues of high lipid content including the myelin sheath in the nervous system. The purpose of this work was to study the evidence that long-term (more than 10 years) exposure to organic solvent mixtures among painters can induce neuro-ophthalmological effects on the function of retinal ganglion cells and the optic tract. Twenty workers with long-term occupational exposure to mixed organic solvents were compared to 40 control subjects. The controls were matched for age, gender, and demographic characteristics but were not occupationally exposed to any known organic solvents, using the following comparators: visual evoked potential (VEP), electroretinogram (ERG), color vision (CV), and contrast sensitivity (CS) testing. Environmental monitoring was done in the work environment with consideration to the American Conference of Governmental Industrial Hygienists Threshold Limit Values (ACGIH-TLVs). The exposed group had significantly longer latency and higher amplitude of VEP waves especially P100, higher Color Confusion Index (CCI), especially affecting the blue-yellow spectrum, and lower Log CS. There was no significant difference between exposed and nonexposed groups in full-field flash ERG response; however, in the pattern ERG, the exposed group had significantly longer latency of P50, which reflects changes in the retinal ganglion cell. Long-term occupational exposure to mixed organic solvents appeared to affect the optic tract functions in the form of increasing latency of VEP response, affecting the quality of CV and decreasing CS. It also affects the retinal ganglion cell layer with increased latency of P50 of the pattern ERG response.

Микроциркуляторные и функциональные изменения в сетчатке и каналах зрительной системы при рассеянном склерозе

Purpose: to compare subtle changes in retinal and optic disk morphology and microcirculation and the functional activity of visual channels in patients with multiple sclerosis (MS) and optical neuritis (ON) in the medical history. Material and methods: 19 patients with remitting MS (duration of about four years) and ON developed about six months ago were tested by standard neurologic and ophthalmologic techniques, optical coherent tomography (OCT) with the angio OCT (RTVue XR 100 Avanti) protocol. The pattern ERG (PERG), as well as visual evoked potentials (VEP), on the reversing black/ white, pure luminance (black/yellow) and chromatic (red/green and blue/yellow) chess stimuli were recorded (RETI-port/ scan, Roland Consult, Germany). Results: At the level of superficial capillary plexus, the density and the area of vessels were reduced in the parafoveal zone, and the blood flow index dropped significantly (to 82.6% against the control). No statistically significant changes of blood flow were found in the peripapillary zone. The peak latency of P50 in the PERG responses to all stimuli showed a statistically significant reduction. The peak latency of N95 was delayed by an average of 10 % as compared to the controls. The amplitude of PERG N95 was moderately reduced for stimuli of all sizes. The elongation of the culmination time for the peak P100 was shown to be significant only in the VEP responses to blue/yellow patterns with angular sizes of 16° and 0.3°. A decrease in the thickness of the ganglion cells (GCC) complex correlated highly with reduced microcirculation in the superficial capillary plexus. Conclusion: Early changes of the retinal function were documented in patients with recent MS and ON history with almost equal involvement of the retinal ganglion cells of the parvo-, mango- and koniocellular systems into the pathological process. For the first time, we established direct correlation between the parameters of microcirculation and morphometry of the inner retina. Clinical significance of the simultaneous detection in MS patients of the delay of P100 latency in the VEP and reduction of the thickness of the SCC and the retinal nerve fiber layer was shown. For citations: Lantukh E.P., Zueva M.V., Tsapenko I.V., et al. Microcirculatory and functional changes in the retina and visual channels in multiple sclerosis. Russian ophthalmological journal. 2017; 10 (3): 29-41. doi: 10.21516/2072-0076-2017-10-3-29-41 (in Russian).

Comparison of multifocal pattern ERG responses to luminance and chromatic contrast stimulations

PurposeTo evaluate the relationship between ganglion cells properties and responses obtained with multifocal pattern ERG.Methods6 normal subjects were tested with 3 types of multifocal ERG stimulations: standard flash, pattern reversal with luminance contrast (black / white) and pattern reversal with chromatic contrast (red / green). The amplitude density and implicit times (ms) of responses were evaluated as a function of eccentricity with respect to fixation.ResultsThe amplitude density of responses was much smaller for pattern reversal stimulations than for flash stimulations with a ratio of 2.5 at the fovea (57 nV/deg2 vs. 146 nV/deg2) and 13 at 15 degrees of eccentricity (3.2 nV/deg2 vs. 43 nV/deg2). The responses to chromatic contrast were significantly delayed in comparison with luminance contrast.ConclusionsThe variation of amplitude density of multifocal ERG responses with eccentricity was found similar to the variation in density of photoreceptors for flash stimulations and of ganglion cells for pattern stimulations.

Retinal Neurodegeneration in db/db Mice at the Early Period of Diabetes.

Purpose. To describe both the functional and pathological alternations in neurosensory retina in a murine model of spontaneous type 2 diabetes (db/db mouse). Methods. db/db (BKS/DB−/−) mice and heterozygous littermates (as control group) at various ages (12, 16, 20, 24, and 28 weeks) were inspected with pattern electroretinogram (PERG), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT). Histological markers of neuroinflammation (IBA-1 and F4/80) were evaluated by immunohistochemistry. In addition, levels of retinal ganglion cell death were measured by terminal dUTP nick-end labeling (TUNEL). Results. Significant alternations of PERG responses and increased retinal ganglion cells (RGCs) apoptosis were observed in diabetic db/db mice for 20-week period when compared with control group. IBA-1 and F4/80 expression in microglia/macrophages became evidently for 24-week period, thus supporting the PERG findings. Furthermore, obvious thinning of nasal and dorsal retina in 28-week-old db/db mice was also revealed by OCT. No visible retinal microvascular changes were detected by FFA throughout the experiments on db/db mice. Conclusions. Diabetic retina underwent neurodegenerative changes in db/db mice, which happened at retinal ganglion cell layer and inner nuclear layer. But there was no obvious abnormality in retinal vasculature on db/db mice.

Rescue of retinal function by BDNF in a mouse model of glaucoma.

Vision loss in glaucoma is caused by progressive dysfunction of retinal ganglion cells (RGCs) and optic nerve atrophy. Here, we investigated the effectiveness of BDNF treatment to preserve vision in a glaucoma experimental model. As an established experimental model, we used the DBA/2J mouse, which develops chronic intraocular pressure (IOP) elevation that mimics primary open-angle glaucoma (POAG). IOP was measured at different ages in DBA/2J mice. Visual function was monitored using the steady-state Pattern Electroretinogram (P-ERG) and visual cortical evoked potentials (VEP). RGC alterations were assessed using Brn3 immunolabeling, and confocal microscope analysis. Human recombinant BDNF was dissolved in physiological solution (0.9% NaCl); the effects of repeated intravitreal injections and topical eye BDNF applications were independently evaluated in DBA/2J mice with ocular hypertension. BDNF level was measured in retinal homogenate by ELISA and western blot. We found a progressive decline of P-ERG and VEP responses in DBA/2J mice between 4 and 7 months of age, in relationship with the development of ocular hypertension and the reduction of Brn3 immunopositive RGCs. Conversely, repeated intravitreal injections (BDNF concentration = 2 µg/µl, volume = 1 µl, for each injection; 1 injection every four days, three injections over two weeks) and topical eye application of BDNF eye-drops (12 µg/µl, 5 µl eye-drop every 48 h for two weeks) were able to rescue visual responses in 7 month DBA/2J mice. In particular, BDNF topical eye treatment recovered P-ERG and VEP impairment increasing the number of Brn3 immunopositive RGCs. We showed that BDNF effects were independent of IOP reduction. Thus, topical eye treatment with BDNF represents a promisingly safe and feasible strategy to preserve visual function and diminish RGC vulnerability to ocular hypertension.

Effects of coenzyme Q10 in conjunction with vitamin E on retinal-evoked and cortical-evoked responses in patients with open-angle glaucoma.

To evaluate pattern-evoked retinal and cortical responses [pattern electroretinogram (PERG) and visual-evoked potential (VEP), respectively] after treatment with coenzyme Q10 in conjunction with vitamin E in open-angle glaucoma (OAG) patients. Forty-three OAG patients (mean age, 52.5±5.29 y; intraocular pressure <18 mm Hg with β-blocker monoterapy only) were enrolled. At baseline and after 6 and 12 months, simultaneous recordings of PERG and VEPs were obtained from 22 OAG patients who underwent treatment consisting of coenzyme Q10 and vitamin E (Coqun, 2 drops/d) in addition to β-blocker monoterapy (GC group), and from 21 OAG patients who were only treated with β-blockers (GP group). At baseline, intraocular pressure, PERG, and VEP parameters were similar in both GC and GP groups (analysis of variance, P>0.05). After 6 and 12 months, PERG and VEP response parameters of GP patients were unchanged when compared to baseline. In GC patients, PERG P50 and VEP P100 implicit times were decreased, whereas PERG P50-N95 and VEP N75-P100 amplitudes were increased (P<0.01) when compared to baseline. In the GC group, the differences in implicit times and amplitudes with respect to baseline were significantly larger (P<0.01) than those recorded in the GP group. The improvement (12 mo minus baseline) of VEP implicit time was significantly correlated with the changes of PERG P50-N95 amplitude (r=-0.66171, P=0.0008) and P50 implicit time (r=0.68364, P=0.00045) over a period of 12 months. Coenzyme Q10 associated with vitamin E administration in OAG shows a beneficial effect on the inner retinal function (PERG improvement) with consequent enhancement of the visual cortical responses (VEP improvement).

Pattern Electroretinograms During the Cold Pressor Test in Normals and Glaucoma Patients

To examine the influence of the cold pressor test (CPT) on steady-state pattern electroretinograms (PERG) in healthy subjects and glaucoma patients. Steady-state PERGs to 7.8 Hz pattern reversal stimuli were recorded in 63 subjects. Fifteen healthy control subjects, 14 patients with ocular hypertension (OHT), and 34 patients with open-angle glaucoma (20 normotensive [NTG] and 14 high tension glaucoma [HTG]) were examined. Steady-state PERG amplitudes and latencies were analyzed at baseline, during cold stimulus using a modified CPT, and during the subsequent recovery phase. Blood pressure and heart rate were simultaneously recorded in 10 normals and 11 glaucoma patients. During the three test conditions (baseline, ice water, and warm water) glaucoma patients (NTG and HTG) showed significantly reduced PERG amplitudes in comparison with control subjects (P < 0.001) and with OHT patients (P < 0.004). Patients with OHT displayed lower PERG amplitudes than control subjects (nonsignificant, with consideration of Bonferroni). Only NTG patients showed a significant effect of the CPT on PERG amplitude (significant decrease during warm water P = 0.02). Latencies shortened significantly during warm-water period after cold stimulus in control subjects (P = 0.05) and in NTG patients (P = 0.02) with a nonsignificant trend of shortened latencies in the OHT (P = 0.06) and HTG groups (P = 0.3). Systolic and diastolic blood pressure increased during cold water (P < 0.001) and decreased during warming-up conditions (P < 0.001). This study shows that a CPT influences the PERG responses particularly in NTG. (ClinicalTrials.gov number, NCT00494923.).

Retinal Function and Neural Conduction Along the Visual Pathways in Affected and Unaffected Carriers With Leber's Hereditary Optic Neuropathy

We assessed retinal ganglion cell (RGC) function, and established a correlation between the neural conduction along the visual pathways and the retinal involvement in Leber's hereditary optic neuropathy (LHON). A total of 39 individuals carrying a LHON mutation (mean age, 33.35 ± 8.4 years), LHON-unaffected (LU, 22 eyes) or LHON-affected (LA, 17 eyes), underwent visual acuity and visual field examinations. A total of 22 age-similar normal subjects (mean age, 38.2 ± 6.0 years) served as controls. In all subjects, simultaneous pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) were recorded in response to 60-minute (60') and 15-minute (15') checkerboard stimuli. When compared to controls, LU eyes did not show any statistically significant difference in 60' and 15' VEP P100 implicit times (ITs), VEP N75-P100 amplitudes, and 60' PERG P50 ITs, whereas 15' PERG P50-N95 amplitudes were significantly (P < 0.01) reduced. When compared to control and LU eyes, LA eyes showed significant differences in PERG and VEP ITs, and amplitudes with both stimulations (60' and 15' checks). No significant correlations between PERG and VEP parameters were found in LU eyes, while in LA eyes, PERG P50 and VEP P100 ITs correlated significantly only when using 60' checks. The LHON-unaffected eyes showed a retinal dysfunction detected by abnormal PERG responses that was not associated with changes along the visual pathways assessed by normal VEP responses. In LA eyes, the impaired neural conduction recorded by VEPs in response to larger (60' VEP responses) and smaller (15' VEP responses) checks were associated and not associated, respectively, with the detected retinal dysfunction.