Electroretinogram Amplitudes Research Articles

Investigating Multimodal Diagnostic Eye Biomarkers of Cognitive Impairment by Measuring Vascular and Neurogenic Changes in the Retina.

Previous studies have demonstrated that cognitive impairment (CI) is not limited to the brain but also affects the retina. In this pilot study, we investigated the correlation between the retinal vascular complexity and neurodegenerative changes in patients with CI using a low-cost multimodal approach. Quantification of the retinal structure and function were conducted for every subject (n = 69) using advanced retinal imaging, full-field electroretinogram (ERG) and visual performance exams. The retinal vascular parameters were calculated using the Singapore Institute Vessel Assessment software. The Montreal Cognitive Assessment was used to measure CI. Pearson product moment correlation was performed between variables. Of the 69 participants, 32 had CI (46%). We found significantly altered microvascular network in individuals with CI (larger venular-asymmetry factor: 0.7 ± 0.2) compared with controls (0.6 ± 0.2). The vascular fractal dimension was lower in individuals with CI (capacity, information and correlation dimensions: D0, D1, and D2 (mean ± SD): 1.57 ± 0.06; 1.56 ± 0.06; 1.55 ± 0.06; age 81 ± 6years) vs. controls (1.61 ± 0.03; 1.59 ± 0.03; 1.58 ± 0.03; age: 80 ± 7 years). Also, drusen-like regions in the peripheral retina along with pigment dispersion were noted in subjects with mild CI. Functional loss in color vision as well as smaller ERG amplitudes and larger peak times were observed in the subjects with CI. Pearson product moment correlation showed significant associations between the vascular parameters (artery-vein ratio, total length-diameter ratio, D0, D1, D2 and the implicit time (IT) of the flicker response but these associations were not significant in the partial correlations. This study illustrates that there are multimodal retinal markers that may be sensitive to CI decline, and adds to the evidence that there is a statistical trend pointing to the correlation between retinal neuronal dysfunction and microvasculature changes suggesting that retinal geometric vascular and functional parameters might be associated with physiological changes in the retina due to CI. We suspect our analysis of combined structural-functional parameters, instead of individual biomarkers, may provide a useful clinical marker of CI that could also provide increased sensitivity and specificity for the differential diagnosis of CI. However, because of our study sample was small, the full extent of clinical applicability of our approach is provocative and still to be determined.

Progranulin protects the mouse retina under hypoxic conditions via inhibition of the Toll‑like receptor‑4‑NADPH oxidase 4 signaling pathway.

To investigate the function of progranulin on the retina under hypoxic conditions, 8-week-old C57BL/6 mice were divided into normal condition and hypoxic condition groups (n=24 mice/group). The hypoxia model was established through intravitreal injection of 9 mM cobalt chloride. Subsequently, 10 mM progranulin and an equal amount of PBS were injected into the right and left eyes, respectively. Photoreceptor function was examined using electroretinogram (ERG) analysis. Morphological alterations were examined using immunofluorescence co-localization, retinal vascular inflammation was examined using the leukostasis assay, and signaling pathways were screened using immunoblotting. The results revealed that ERG amplitude was significantly lower under hypoxic conditions compared with under normal conditions. Furthermore, the amplitude was significantly reduced in the PBS-injected eyes compared with in the progranulin-injected eyes. Morphological examination demonstrated that the number of rods in the PBS-injected eyes was decreased compared with in the progranulin-injected eyes under hypoxic conditions. In addition, the arrangement of the cones was sparse and the morphology of the outer segments was short and small. Although the number of adherent leukocytes in the progranulin-injected eyes was higher in the hypoxic mice compared with in those under normal conditions, the number was only 52.31% of the number detected in the PBS-injected eyes. Analysis of the signaling pathways demonstrated that the protective effects of progranulin on retinas under hypoxic conditions were regulated by the Toll-like receptor 4 (TLR4)-NADPH oxidase 4 (NOX4) pathway, instead of the caspase and Wnt/β-catenin pathways. In conclusion, progranulin exerted protective effects on the function and morphology of photoreceptors in a hypoxic environment, and could reduce retinal vascular inflammation, through inhibition of the TLR4-NOX4 pathway.

Foveal amplitudes of multifocal electroretinograms are larger following full-field electroretinograms.

The clinical standards for multifocal electroretinograms (mfERG) call for adaption to normal room lighting before the mfERG begins. They specify that any assessments where bright lights are used, should be done after the mfERG to prevent excess stimulation of retinal cells. However, full-field electroretinograms (FFERG) are performed prior to mfERGs in some clinical settings. It is unclear from the literature whether the FFERG has an impact on the mfERG. This study seeks to examine the effect of the FFERG on the mfERG when performed sequentially. Thirty young healthy subjects (age 27.1 ± 3.5years) were included. Patients reported for two visits and were fully dilated at both visits. At visit one, a FFERG was recorded (VERIS 6.2) using our clinical protocol which includes an ISCEV standard flash sequence; each flash condition was repeated 4-6 times. Following the FFERG, an mfERG was recorded using a 4-min m-sequence at near 100% contrast. At visit two, only the mfERG was recorded. A Burian-Allen contact lens electrode filled with celluvisc was used for all recordings. The two mfERGs were compared for foveal, peripheral, and overall implicit time (IT) and amplitudes (amp). Paired t tests were used to evaluate the data. Coefficient of variation and Bland-Altman analysis was also reported for this patient group. There was a small but statistically significant difference in foveal amplitudes (amp) (p = 0.004) wherein the amp was larger following the FFERG stimuli. The mean difference was 11.1nV/deg2 (100.9nV vs 89.8nV). There was no difference in foveal IT (p = 0.66). There was no difference in overall IT or amp when averaging the entire eye (p = 0.44 amp and p = 0.54 IT) or just evaluating the periphery (p = 0.87 amp and p = 0.051 IT). Bland-Altman analysis found a coefficient of repeatability overall was 1.57ms (IT) and 10.7nV/deg2 (amp). The difference in foveal amplitude is likely the result of a small long-term cone adaptation, but further studies are needed. While it is statistically significant, the small difference is unlikely to be clinically important. These results should help increase clinical confidence in mfERG results when recorded following a FFERG.

Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice.

Fascin2 (FSCN2) is an actin cross-linking protein that is mainly localized in retinas and in the stereocilia of hair cells. Earlier studies showed that a deletion mutation in human FASCIN2 (FSCN2) gene could cause autosomal dominant retinitis pigmentosa. Recent studies have indicated that a missense mutation in mouse Fscn2 gene (R109H) can contribute to the early onset of hearing loss in DBA/2J mice. To explore the function of the gene, Fscn2 was knocked out using TALEN (transcription activator-like effector nucleases) on the C57BL/6J background. Four mouse strains with deletions of 1, 4, 5, and 41 nucleotides in the target region of Fscn2 were developed. F1 heterozygous (Fscn2+/−) mice carrying the same deletion of 41 nucleotides were mated to generate the Fscn2−/− mice. As a result, the Fscn2−/− mice showed progressive hearing loss, as measured in the elevation of auditory brainstem-response thresholds. The hearing impairment began at age 3 weeks at high-stimulus frequencies and became most severe at age 24 weeks. Moreover, degeneration of hair cells and loss of stereocilia were remarkable in Fscn2−/− mice, as revealed by F-actin staining and scanning electron microscopy. Furthermore, compared to the controls, the Fscn2−/− mice displayed significantly lower electroretinogram amplitudes and thinner retinas at 8, 16, and 24 weeks. These results demonstrate that, in C57BL/6Jmice, Fscn2 is essential for maintaining ear and eye function and that a null mutation of Fscn2 leads to progressive hearing loss and retinal degeneration.

Ciliary neurotrophic factor (CNTF) protects retinal cone and rod photoreceptors by suppressing excessive formation of the visual pigments

The retinal pigment epithelium (RPE)-dependent visual cycle provides 11-cis-retinal to opsins in the photoreceptor outer segments to generate functional visual pigments that initiate phototransduction in response to light stimuli. Both RPE65 isomerase of the visual cycle and the rhodopsin visual pigment have recently been identified as critical players in mediating light-induced retinal degeneration. These findings suggest that the expression and function of RPE65 and rhodopsin need to be coordinately controlled to sustain normal vision and to protect the retina from photodamage. However, the mechanism controlling the development of the retinal visual system remains poorly understood. Here, we show that deficiency in ciliary neurotrophic factor (CNTF) up-regulates the levels of rod and cone opsins accompanied by an increase in the thickness of the outer nuclear layers and the lengths of cone and rod outer segments in the mouse retina. Moreover, retinoid isomerase activity, expression levels of RPE65 and lecithin:retinol acyltransferase (LRAT), which synthesizes the RPE65 substrate, were also significantly increased in the Cntf-/- RPE. Rod a-wave and cone b-wave amplitudes of electroretinograms were increased in Cntf-/- mice, but rod b-wave amplitudes were unchanged compared with those in WT mice. Up-regulated RPE65 and LRAT levels accelerated both the visual cycle rate and recovery rate of rod light sensitivity in Cntf-/- mice. Of note, rods and cones in Cntf-/- mice exhibited hypersusceptibility to light-induced degeneration. These results indicate that CNTF is a common extracellular factor that prevents excessive production of opsins, the photoreceptor outer segments, and 11-cis-retinal to protect rods and cones from photodamage.

17β-estradiol ameliorates oxidative stress and blue light-emitting diode-induced retinal degeneration by decreasing apoptosis and enhancing autophagy.

PurposeThis study aimed to assess the effects of 17β-estradiol (βE2) on blue light-emitting diode (LED)-induced retinal degeneration (RD) in rats and hydrogen peroxide (H2O2)-induced retinal pigment epithelium cell injury in humans and elucidate the protective mechanism of βE2 underlying these processes.MethodsFemale ovariectomized (OVX) rats were intravitreally injected with βE2 before blue LED exposure (3,000 lux, 2 hours). Retinal function and morphology were assayed via electroretinogram (ERG) and H&E, respectively. Cell viability was assayed using the Cell Counting Kit-8. Cell ROS were measured using dichlorofluorescein fluorescence. Apoptosis was evaluated by TUNEL and Annexin V/propidium iodide staining. Gene expression and protein expression were quantified using quantitative real-time RT-PCR, Western blotting, and immunohistochemistry. Autophagosomes were examined by electron microscopy.ResultsFemale OVX rats were exposed to blue LED, inducing RD. βE2 significantly prevented the reduction in the a- and b-wave ERG amplitudes and the disruption of retinal structure, the loss of photoreceptor cells, and the decrease in the thickness of the outer nuclear layer caused by blue LED exposure. βE2 also decreased cell apoptosis in the retina in blue LED-induced RD. Additionally, βE2 reduced ROS levels and apoptosis in H2O2-treated human retinal pigment epithelial (ARPE-19) cells. Furthermore, βE2 increased the protein expression of p-Akt and Bcl-2 and decreased the protein expression of cleaved caspase-3 and Bax during blue LED-induced retinal damage and in H2O2-treated ARPE-19 cells. βE2 also increased the number of autopha-gosomes and upregulated the expression of LC3-II/LC3-I and Beclin 1 in these processes.ConclusionβE2 protects against blue LED-induced RD and H2O2-induced oxidative stress by acting as an antioxidant, and its protective mechanism might occur by reducing apoptosis and enhancing autophagy; βE2 may be a novel and effective therapy for age-related macular degeneration.

The role of cystoid macular edema as a marker in the progression of non-paraneoplastic autoimmune retinopathy.

To determine the relationship between cystoid macular edema (CME) and disease severity and progression in non-paraneoplastic autoimmune retinopathy (npAIR). A retrospective study was conducted on patients seen between 2008 and 2016 with npAIR as defined by electroretinogram (ERG) dysfunction, visual field changes, presence of antiretinal antibodies, a negative malignancy workup, and no other apparent cause for visual dysfunction. Optical coherence tomography (OCT) scans were reviewed for each patient. A minimum follow-up of 1year was necessary for study inclusion. The presence or absence of CME and the length of the preserved EZ on the centermost line scan of the SD-OCT images was recorded at each visit. The main outcome measure assessed was the rate of EZ loss (EZ final - EZ initial/days follow-up) over time, a marker for disease progression. Thirty-two eyes (16 patients) were included with an average follow-up of 42months. Twenty-one eyes (66%) had CME on initial presentation and final follow-up (group 1), eight eyes (25%) did not have CME on presentation or final follow-up (group 2), and three eyes (9%) did not have CME on presentation but developed CME during follow-up (group 3). Group 1 eyes had a lower maximal a-wave amplitude (59.0 vs. 220.9mV, p = 0.012) and lower maximal b-wave amplitude (88.1 vs 256.9mV, p = 0.017) on baseline ERG compared to Group 2 eyes. The rate of EZ loss over time was significantly greater for group 1 with CME compared to group 2 without CME both at 12months (- 1.26μm/day vs. - 0.26μm/day, p = 0.022) and at final follow-up (- 1.03μm/day vs. - 0.08μm/day, p = 0.012). CME was associated with decreased ERG amplitudes and greater velocity of EZ loss, suggesting that CME is a useful biomarker of more severe and more progressive disease in npAIR.

Brilliant Blue G protects against photoreceptor injury in a murine endotoxin-induced uveitis model

We previously reported that P2X7 receptor antagonists prevented the retinal injury caused by N-methyl-d-aspartic acid. It has been reported that activation of P2X7 receptor is involved in the secretion of proinflammatory cytokines by macrophages, monocytes, and microglia. Although retinal inflammation is known to cause photoreceptor cell death, it is unclear whether a noncompetitive antagonist of P2X7 receptor can protect photoreceptor cells against inflammation-induced injury. We examined whether Brilliant Blue G (BBG), a potent non-competitive antagonist of P2X7 receptor, had neuroprotective effects on photoreceptor cell injury in a murine endotoxin-induced uveitis (EIU) model. EIU was evoked by lipopolysaccharides (LPS; 10 mg/kg/day) administered intraperitoneally once a day for 4 days. BBG (50 mg/kg/day) and indomethacin (10 mg/kg) were also injected intraperitoneally just before LPS injection. BBG significantly prevented photoreceptor cell loss and reduction of the amplitudes of dark-adapted and light-adapted flush electroretinograms induced by LPS, whereas indomethacin did not show such protective effects. These results indicated that BBG is protective against photoreceptor cell injury in EIU in the mice in vivo, suggesting that P2X7 receptor antagonists may be good candidates for preventing photoreceptor degeneration induced by inflammation.

Effect of varying skin surface electrode position on electroretinogram responses recorded using a handheld stimulating and recording system

PurposeA handheld device (the RETeval system, LKC Technologies) aims to increase the ease of electroretinogram (ERG) recording by using specially designed skin electrodes, rather than corneal electrodes. We explored effects of electrode position on response parameters recorded using this device.MethodsHealthy adult twins were recruited from the TwinsUK cohort and underwent recording of light-adapted flicker ERGs (corresponding to international standard stimuli). In Group 1, skin electrodes were placed in a “comfortable” position, which was up to 20 mm below the lid margin. For subsequent participants (Group 2), the electrode was positioned 2 mm from the lid margin as recommended by the manufacturer. Amplitudes and peak times (averaged from both eyes) were compared between groups after age-matching and inclusion of only one twin per pair. Light-adapted flicker and flash ERGs were recorded for an additional 10 healthy subjects in two consecutive recording sessions: in the test eye, electrode position was varied from 2 to 10–20 mm below the lid margin between sessions; in the fellow (control) eye, the electrode was 2 mm below the lid margin throughout. Amplitudes and peak times (test eye normalised to control eye) were compared for the two sessions.ResultsIncluding one twin per pair, and age-matching yielded 28 individuals per group. Flicker ERG amplitudes were significantly lower for Group 1 than Group 2 participants (p = 0.0024). However, mean peak times did not differ between groups (p = 0.54). For the subjects in whom electrode position was changed between recording sessions, flash and flicker amplitudes were significantly lower when positioned further from the lid margin (p < 0.005), but peak times were similar (p > 0.5).ConclusionsMoving the skin electrodes further from the lid margin significantly reduces response amplitudes, highlighting the importance of consistent electrode positioning. However, this does not significantly affect peak times. Thus, it may be feasible to adopt a more comfortable position in participants who cannot tolerate the recommended position if analysis is restricted to peak time parameters.

Influence of standard corneal cross-linking in keratoconus patients on macular profile

PurposeTo determine the effect of corneal cross-linking (CXL) on retinal structure and function. MethodsThe current study was conducted on 42 eyes of 21 patients with keratoconus (KCN) who were candidates for CXL due to disease progression. The Optovue optical coherence tomography (OCT) (Optovue Inc., Fremont, USA) from macula and multifocal electroretinography (mERG) were performed on all patients prior to surgery and at 1- and 6- month follow-up. Structural and functional parameters of macula including retinal thickness in OCT, and amplitude and latency of electroretinogram were compared between eyes that underwent surgery and control fellow eyes during the study period. ResultsA statistically significant increase in central foveal, foveal, parafoveal, and perifoveal thickness was observed at 1-month follow-up. The changes were non-significant at 6 months. Although a statistically significant reduction in amplitude and increase in latency in both rings 2 and 3 were observed at 1 month in mERG, only amplitude changes in ring 2 remained significant at 6 months. ConclusionTransient anatomical and functional alterations following CXL were observed in the current study.

Application of empirical Bayes methods to predict the rate of decline in ERG at the individual level among patients with retinitis pigmentosa.

Retinitis pigmentosa is one of the most common forms of inherited retinal degeneration. The electroretinogram (ERG) can be used to determine the severity of retinitis pigmentosa-the lower the ERG amplitude, the more severe the disease is. In practice for career, lifestyle, and treatment counseling, it is of interest to predict the ERG amplitude of a patient at a future time. One approach is prediction based on the average rate of decline for individual patients. However, there is considerable variation both in initial amplitude and in rate of decline. In this article, we propose an empirical Bayes (EB) approach to incorporate the variations in initial amplitude and rate of decline for the prediction of ERG amplitude at the individual level. We applied the EB method to a collection of ERGs from 898 patients with 3 or more visits over 5 or more years of follow-up tested in the Berman-Gund Laboratory and observed that the predicted values at the last (kth) visit obtained by using the proposed method based on data for the first k-1 visits are highly correlated with the observed values at the kth visit (Spearman correlation =0.93) and have a higher correlation with the observed values than those obtained based on either the population average decline rate or those obtained based on the individual decline rate. The mean square errors for predicted values obtained by the EB method are also smaller than those predicted by the other methods.

Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina.

Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O-glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. Highlights: The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut (Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms.

Association of Vitamin A Supplementation With Disease Course in Children With Retinitis Pigmentosa

While oral vitamin A supplementation is considered to potentially slow loss of retinal function in adults with retinitis pigmentosa and normal liver function, little data from children with this disease are available. To compare disease courses in children with retinitis pigmentosa taking or not taking vitamin A supplementation. Retrospective, nonrandomized comparison of vitamin A and control cohorts followed up for a mean of 4 to 5 years by the Electroretinography Service of the Massachusetts Eye and Ear Infirmary. The study included children with different genetic types of typical retinitis pigmentosa: 55 taking vitamin A and 25 not taking vitamin A. The dates for patient evaluations ranged from June 1976 to July 2016, and the data analysis occurred in October 2016. Age-adjusted dose of oral vitamin A palmitate (≤15 000 IU/d). Mean exponential rates of change of full-field cone electroretinogram amplitude to 30-Hz flashes estimated by repeated-measures longitudinal regression without and with adjusting for potential confounders. Of the 55 children in the vitamin A cohort, 38 (69%) were male; the mean [SD] age was 9.1 [1.9] years; and 48 (87%) were white , 6 (11%) were Asian, and 1 (2%) was black. Of the 25 members of the control cohort, 19 (76%) were male; the mean [SD] age was 9.2 [1.7] years; and 25 (100%) were white. The estimated mean rates of change with the unadjusted model were -0.0713 loge unit/y (-6.9% per year) for the vitamin A cohort and -0.1419 loge unit per year (-13.2% per year) for the control cohort (difference, 0.0706 loge unit per year; 95% CI for the difference, 0.0149-0.1263 loge unit per year; P = .01). The adjusted model confirmed a slower mean rate of decline in the vitamin A cohort (difference, 0.0771 loge-unit per year; 95% CI for the difference, 0.0191-0.1350 loge-unit per year; P = .009). With respect to ocular safety, the mean exponential rates of change of visual field area and visual acuity and the incidences of falling to a visual field diameter of 20° or less or a visual acuity of 20/200 or less in at least 1 eye did not differ by cohort. A vitamin A palmitate supplement was associated with a slower loss of cone electroretinogram amplitude in children with retinitis pigmentosa. Although the relatively small-sample, retrospective, nonrandomized design does not allow a test of causation and is subject to possible biases, these findings support consideration of an age-adjusted dose of vitamin A in the management of most children with the common forms of retinitis pigmentosa.

The Complement System Is Critical in Maintaining Retinal Integrity during Aging.

The complement system is a key component of innate immunity comprised of soluble components that form a proteolytic cascade leading to the generation of effector molecules involved in cellular clearance. This system is highly activated not only under general inflammatory conditions such as infections, collagen diseases, nephritis, and liver diseases, but also in focal ocular diseases. However, little is known about the role of the complement system in retinal homeostasis during aging. Using young (6-week-old) and adult (6-month-old) mice in wild type (C57BL/6) and complement knockout strains (C1q−/−, Mbl a/c−/−, Fb−/−, C3−/−, and C5−/−), we compared amplitudes of electroretinograms (ERG) and thicknesses of retinal layers in spectral domain optical coherence tomography between young and adult mice. The ERG amplitudes in adult mice were significantly decreased (p < 0.001, p < 0.0001) compared to that of young mice in all complement knockout strains, and there were significant decreases in the inner nuclear layer (INL) thickness in adult mice compared to young mice in all complement knockout strains (p < 0.0001). There were no significant differences in ERG amplitude or thickness of the INL between young and adult control mice. These data suggest that the complement system plays an important role in maintaining normal retinal integrity over time.

Pharmacological correction of retinal ischemia/reperfusion by minoxidil

Introduction/Objective. The objective of this paper was to increase the effectiveness of pharmacological correction of retinal ischemia-reperfusion by using minoxidil. Methods. The research was carried out on 180 Wistar rats. A modification of the retinal ischemia-reperfusion model was used, in which an increase in intraocular pressure is carried out by mechanical pressure (110 mmHg) to the front chamber of the eye for 30 minutes. Protective effects of minoxidil at a dose 0.5 mg/kg on the model of retinal ischemia-reperfusion were estimated by the changes in the level of retinal microcirculation (laser Doppler flowmetry), electroretinogram amplitude, morphometry of retinal layers after 1 hour and 72 hours of reperfusion. Results. Minoxidil at a dose 0.5 mg/kg of rat mass improves retinal microcirculation, its electrophysiological state after 1 hour and 72 hours of reperfusion, and prevents the development of degenerative changes in the retina caused by ischemic damage to a greater extent than recombinant erythropoietin at a dose of 50 IU/kg and sildenafil at a dose of 0.5 mg/kg in monotherapy. The protective effects of minoxidil were eliminated by the preliminary administration of glibenclamide at a dose of 5 mg/kg, which indicates the presence of the preconditioning effect of minoxidil, realized through adenosine triphosphate-dependent potassium channels. Conclusion. Minoxidil at a dose of 0.5 mg/kg of rat mass protects the retina from ischemic-reperfusion injury. Protective effects of minoxidil are carried out by a preconditioning action, as evidenced by the lack of positive effects with the administration of glibenclamide.

Therapeutic potential of valproic acid in advanced glaucoma: A pilot study.

Purpose:Oral valproic acid (VPA) used as an anticonvulsant has been shown to improve contrast threshold sensitivities in patients receiving it on long-term. This study aimed to evaluate the efficacy of oral VPA in improving visual function in eyes with advanced stage glaucoma.Methods:In this prospective randomized study, 31 patients (n = 31 eyes) with advanced stage glaucoma (with an intraocular pressure <16 mmHg) in at least one eye received oral VPA 500 mg once a day for 3 months and 33 patients (n = 33 eyes) continued on glaucoma therapy. Patients were followed up at 3 and 12 months (to evaluate the legacy effect of the drug). Blood VPA concentrations were measured at 3 months. Following parameters were assessed at baseline, 3 months and 12 months: log of the minimum angle of resolution (LogMAR) visual acuity, mean deviation on visual fields, and multifocal electroretinogram (ERG).Results:Median LogMar visual acuity in the VPA group improved from 0.3 at baseline to 0.18 and 0.18 at 3 and 12 months, respectively (P < 0.01). In comparison, the median visual acuity in control group at baseline was 0.18 and showed neither worsening nor improvement over 3 and 12 months (P = 0.56). The improvement in VPA group was significant compared to the control group (P < 0.01; Wilcoxon Signed-rank test). An improvement in one line was experienced in 11 out of 31 eyes in the VPA group compared to 1 out of 33 eyes among controls (P = 0.003). No significant improvement was noted in the mean deviation, and the multifocal ERG (Latency and amplitudes) in the VPA-treated patients. The average blood VPA concentration measured at 3 months of therapy was 26 ± 8.9 μg/ml (range 8–55 μg/ml) which is much lower than that achieved during anticonvulsant therapy. None of the patients complained of any adverse effects that required stopping VPA therapy.Conclusion:A 3 months oral VPA therapy results in some improvement in visual acuity in a subgroup of eyes with advanced glaucoma and the effect was seen to persist 9 months after the drug was stopped.

Ophthalmic Formulation Containing Nilvadipine Nanoparticles Prevents Retinal Dysfunction in Rats Injected with Streptozotocin.

Retinopathy leads to irreparable vision loss via capillary closure and areas of nonperfusion. However, the current instillation systems do not allow a sufficient amount of drug required to treat retinopathy to reach the posterior segment (retina); therefore, a new formulation targeting the posterior segment is expected as therapy for retinopathy. We prepared ophthalmic formulations containing nilvadipine nanoparticles (NILnano), and demonstrated whether the instillation of NILnano can prevent retinal dysfunction in rats injected with excessive streptozotocin (STZ rats) in this study. NILnano (mean particle size, 77 nm) was prepared by wet bead mill treatment, with the inclusion of various additives (2-hydroxypropyl-β-cyclodextrin, benzalkonium chloride, d-mannitol, and methylcellulose). Retinal dysfunction was observable two weeks after rats received intraperitoneal injections of streptozotocin (100 mg/kg × 2, consecutive days, STZ rat). Changes in retinal function were evaluated by electroretinogram (ERG) and immunological methods. The retinal thickness, measured as the distance between the ganglion cell layer and the distal border of the outer nuclear layer, increased two weeks after the injection of streptozotocin, resulting in decreases in the levels of a-waves, b-waves, and oscillatory potential amplitudes in ERG of rats. The instillation of NILnano allowed the topical supplement of nilvadipine into the retina, and repeated instillation of NILnano (2 times/day) attenuated the retinal disorders led by the excessive streptozotocin. In conclusion, we found that retinal dysfunction in rats injected with streptozotocin can be prevented by the NILnano instillation. These results are useful in further studies aimed at the therapeutic treatment of retinopathy.

Event-Related Potentials in the Visual Center of the Carp on Application of Baclofen to the Retina

The effects of activation of retinal GABAB receptors with baclofen on event-related potentials (ERP) arising in the primary visual center (the tectum) on illumination of the retina with white light and on electrical stimulation of the optic nerve were studied in dark-adapted carp. These studies showed that baclofen-induced decreases in the amplitude of the electroretinogram (ERG) b wave were accompanied by increases in ERP amplitude both to light stimuli and to electrical stimulation of the optic nerve. It is suggested that this increase is due to an increase in the response of tertiary retinal neurons to light and/or an increase in the excitability of tectum neurons due to a reduction in tonic influences from the visual afferent stream.

Preparation and Evaluation of Biodegradable Scleral Plug Containing Curcumin in Rabbit Eye

ABSTRACTBackground: To test whether biodegradable curcumin-loaded scleral plug is a promising choice for treating posterior ocular diseases, the study investigated the in vitro release profile of the scleral plug and its safety in vivo.Methods: Scleral plugs containing 0.5 mg, 1.0 mg and 1.5 mg curcumin were synthesized by a compression-sintering method. These scleral plugs were placed in tubes containing balanced salt solution (BSS) buffer, which was replaced by fresh buffer daily. The curcumin concentration in the removed aliquot was tested daily for 14 days using high-performance liquid chromatography (HPLC). In the study, 44 rabbits were randomly divided into four groups: control, 0.5 mg, 1.0 mg and 1.5 mg curcumin groups. The scleral plug was trans-scleral fixed in the right eye of the rabbits in the three curcumin-treated groups. The control rabbits only received sclerotomy. The treated rabbit eyes were examined by a slit-lamp biomicroscope, an indirect ophthalmoscope and electroretinogram (ERG), and subjected to histological analysis.Results: The concentration of the 1.5 mg curcumin-loaded scleral plug was higher than 15 μg/ml for consecutive 14 days in vitro. The in vivo experiments revealed intraocular pressure, a-wave and b-wave amplitudes of ERG, and conjunctival reaction degree were not significantly different between the four groups. Retinal structure was normal in the curcumin-treated groups. The sclerotomy wound healed after the plug was completely degraded. Anterior chamber reaction or complications were not observed.Conclusion: The study suggests that curcumin-loaded scleral plug could sustain high concentration of curcumin in vitro and is safe in vivo. It might be a promising alternative choice for the treatment of posterior ocular diseases.

Genetic testing for retinitis punctata albescens/fundus albipunctatus

Abstract We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for retinitis punctata albescens/fundus albipunctatus (RPA/FA). RPA and FA are reported to have autosomal dominant or autosomal recessive inheritance and are associated with variations in the PRPH2, RHO, RLBP1 and RDH5 genes. There is insufficient data to establish their prevalence. Clinical diagnosis is based on clinical findings, ophthalmological examination, optical coherence tomography, visual field testing and undetectable or severely reduced electroretinogram amplitudes. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.