Retinal and cortical visual acuity in a common inbred albino mouse.
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ABSTRACT:
SUBMITTER: Braha M
PROVIDER: S-EPMC8162811 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Intellectual disability (ID) is a neurodevelopmental disorder affecting approximately 0.5-3% of the population in the developed world. Individuals with ID exhibit deficits in intelligence and impaired adaptive behavior, frequently as well as visual impairments. Cytoplasmic FMR1-interacting protein 2 (CYFIP2) is an interacting partner of fragile X mental retardation protein, whose loss results in fragile X syndrome, the most common inherited cause of ID. Recently, CYFIP2 variants were found in patients with early-onset epileptic encephalopathy, developmental delay, and ID. Individuals with these CYFIP2 variants often exhibit visual impairments, however, the underlying mechanism is poorly understood. In the current study, we investigated the role of Cyfip2 in retinal and visual function by generating and analyzing mice in which Cyfip2 is depleted in the retina (Cyfip2 CKO mice). We found no major difference in the layer structure and cell composition between control and Cyfip2 CKO retinas, whereas a subset of genes associated with transporter and channel activity was differentially expressed in the Cyfip2 CKO retina. Multi-electrode array recordings showed more sustained and stronger response to positive flashes of ON ganglion cells in the Cyfip2 CKO retina, although we did not observe that Cyfip2 deficiency affects photoreceptor and ON bipolar cell functions by electroretinogram analysis. Furthermore, initial and late phase OKR analysis demonstrated that Cyfip2 deficiency impairs visual function at the organismal level. Together, our results shed light on the molecular mechanism underlying visual impairments observed in individuals with CYFIP2 variants and, more generally, in patients with neurodevelopmental disorders including ID.
2021-09-12 | GSE176528 | GEO
Project description:In the developing murine eye, melanin synthesis in the retinal pigment epithelium (RPE) coincides with neurogenesis of retinal ganglion cells (RGCs). Disruption of pigmentation in the albino RPE is associated with delayed neurogenesis in the ventrotemporal retina, the source of ipsilateral RGCs, and a reduced ipsilateral RGC projection. To begin to unravel how melanogenesis and the RPE regulate RGC neurogenesis and cell subpopulation specification, we compared the features of albino and pigmented mouse RPE cells during the period of RGC neurogenesis (embryonic day, E, 12.5 to 18.5) when the RPE is closely apposed to developing RGC precursors. At E12.5 and E15.5, although albino and pigmented RPE cells express RPE markers Otx2 and Mitf similarly, albino RPE cells are irregularly shaped and have fewer melanosomes compared with pigmented RPE cells. The adherens junction protein P-cadherin appears loosely distributed within the albino RPE cells rather than tightly localized on the cell membrane, as in pigmented RPE. Connexin 43 (gap junction protein) is expressed in pigmented and albino RPE cells at E13.5 but at E15.5 albino RPE cells have fewer small connexin 43 puncta, and a larger fraction of phosphorylated connexin 43 at serine 368. These results suggest that the lack of pigment in the RPE results in impaired RPE cell integrity and communication via gap junctions between RPE and neural retina during RGC neurogenesis. Our findings should pave the way for further investigation of the role of RPE in regulating RGC development toward achieving proper RGC axon decussation. J. Comp. Neurol. 524:3696-3716, 2016. © 2016 Wiley Periodicals, Inc.
| S-EPMC5063670 | biostudies-literature
Project description:Purpose:To determine whether disorganization of retinal inner layers (DRIL) on optical coherence tomography (OCT) is associated with ischemia on ultra-widefield fluorescein angiography (UWFFA) and with visual outcomes in eyes with acute, treatment-naïve central retinal vein occlusion (CRVO). Design:Retrospective, single-institution, longitudinal cohort study. Participants:Twenty-five consecutive patients with treatment-naïve CRVO and ? 1 year follow-up. Methods:Two independent masked graders evaluated the extent of DRIL, ellipsoid zone disruption, external limiting membrane disruption, and other OCT parameters at the baseline, 6- month, 12-month, and final visits. Baseline UWFFA images were assessed for ischemic index values and foveal avascular zone (FAZ) enlargement. Main Outcome Measures:Associations of DRIL with UWFFA findings and clinical outcomes including corrected visual acuity (VA). Results:The median time to final follow-up was 24 months (range 12.1 - 43.9 months). Median DRIL extent at baseline was 765 µm (range 0 - 1000 µm). Eighteen of 25 eyes (72%) had some degree of DRIL at baseline, and 20 of 25 eyes (80%) had cystoid macular edema (CME). Neither the presence nor extent of DRIL at baseline was associated with presenting VA. In a cross-sectional analysis of each visit, extent of DRIL correlated with worse VA at both the 6-month (? = 0.656; p = 0.001) and final (? = 0.509; p = 0.016) visits. At final follow-up, DRIL extent was the OCT parameter most strongly correlated with baseline ischemic index (? = 0.418; p = 0.047) and baseline enlarged FAZ (p = 0.057) on UWFFA. On multivariate regression analysis, DRIL extent at final follow-up was the only OCT parameter associated with worse VA (p = 0.013) and remained significant when accounting for CME as a potential confounder. Conclusions:Extent of DRIL was not associated with presenting VA in treatment-naïve eyes with acute CRVO. Following six months of follow-up however, DRIL extent correlated with worse VA and was predictive of worse VA throughout more than 2 years of follow-up. Ischemic features on UWFFA at baseline are predictive of the extent of DRIL development at final follow-up.
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Project description:Purpose:The purpose of this study was to measure alterations of inner retinal microvascular density and outer retinal sublayer thicknesses in pathological myopia, and to correlate the measured parameters with best corrected visual acuity (BCVA). Methods:Optical coherence tomography (OCT) and OCT angiography (OCTA) images of 21 control, 48 simple high myopia, and 22 pathological myopia eyes were analyzed to quantify the thicknesses of the outer retinal sublayers and the density of the inner retinal microvascular network that includes the superficial retinal capillary plexus (SRCP) and deep retinal capillary plexus (DRCP). Retinal sublayer thicknesses and microvascular densities were compared among the three groups, and correlations of sublayer thicknesses and microvascular densities with BCVA were determined. Results:In pathological myopia, density of the DRCP, thicknesses of myoid and ellipsoid zone (MEZ), interdigitation zone and retinal pigment epithelium/Bruch complex (IZ + RPE), and choroid were lower than in simple high myopia (P < 0.05). The decreased DRCP density was correlated with thinner MEZ and IZ+RPE in pathological myopia (P < 0.05), but not in simple high myopia (P > 0.05). Simple linear regression showed that axial length, female, thicknesses of outer plexiform layer (OPL), MEZ, IZ + RPE, choroid, and density of the SRCP and DRCP were correlated with BCVA. In multiple regression analysis, worse BCVA was associated only with thinner MEZ, thinner choroid, and decreased DRCP (P < 0.05). Conclusions:Alteration of inner retinal microvascular density and outer retinal sublayer thicknesses occurred in pathological myopia, especially decreased DRCP and thinner MEZ, which were significantly associated with worse BCVA.
| S-EPMC7401930 | biostudies-literature
Project description:Recently, there have been increasing indications that the endocannabinoid (eCB) system is involved in vision. Multiple research teams studied the cannabinoid receptor type 2 (CB2R) expression and function in the mouse retina. Here, we examined the consequence of CB2R modulation on visual acuity using genetic and pharmacologic tools. We found that Cnr2 knockout mice show an enhanced visual acuity, CB2R activation decreased visual acuity while CB2R blockade with the inverse agonist AM630 increased it. The inhibition of 2-arachidonylglycerol (2-AG) synthesis and degradation also greatly increased and decreased visual acuity, respectively. No differences were seen when the cannabinoid receptor type 1 (CB1R) was deleted, blocked or activated implying that CB2R exclusively mediates cannabinoid modulation of the visual acuity. We also investigated the role of cannabinoids in retinal function using electroretinography (ERG). We found that modulating 2-AG levels affected many ERG components, such as the a-wave and oscillatory potentials (OPs), suggesting an impact on cones and amacrine cells. Taken together, these results reveal that CB2R modulates visual acuity and that eCBs such as 2-AG can modulate both visual acuity and retinal sensitivity. Finally, these findings establish that CB2R is present in visual areas and regulates vision-related functions.
| S-EPMC7519129 | biostudies-literature
Project description:BACKGROUND:To identify baseline patient characteristics associated with early clinically significant visual acuity (VA) improvements within 3?months of treatment initiation in ranibizumab-treated patients with retinal vein occlusion (RVO) in the SHORE study. METHODS:Post hoc analysis of baseline patient characteristics in the randomized, open-label, vision examiner-masked SHORE phase 4 study that compared monthly versus pro re nata dosing of ranibizumab in patients with branch and central RVO. Patients who enrolled in SHORE fulfilled eligibility criteria per protocol (N =?202). SHORE data were retrospectively analyzed to identify baseline patient characteristics associated with early clinically significant improvements in VA, defined as improvement to a Snellen equivalent of 20/40 or better vision (? 69 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) or an increase in best-corrected VA (BCVA) of 15 or more ETDRS letters from baseline within 3?months of treatment initiation. Main outcome measures were BCVA gain of 15 or more ETDRS letters from baseline, Snellen equivalent of 20/40 or better vision, and baseline factors associated with early clinically significant improvement in BCVA. RESULTS:The median time for patients to achieve a BCVA of 20/40 or better was 59?days and the median time for patients to gain 15 or more ETDRS letters was 63?days. Better baseline BCVA (>?50 ETDRS letters/Snellen equivalent ??20/100), greater baseline total macular volume (>?9.99?mm3), and presence of subretinal fluid at baseline were all associated with early improvement to 20/40 or better vision (ETDRS equivalent ??69 letters; P <?.0001, P =?.02, and P =?.03, respectively). CONCLUSIONS:This retrospective analysis found that better BCVA, greater total macular volume, and presence of subretinal fluid at baseline were associated with more rapid vision gains. Clinicians may find these helpful when considering the likelihood of achieving early clinically significant VA improvements with ranibizumab in patients with RVO. TRIAL REGISTRATION:ClinicalTrials.gov NCT01277302 .
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Project description:PurposeTo evaluate the association between ellipsoid zone (EZ) on spectral domain optical coherence tomography (SD-OCT) and visual acuity letter score (VALS) in participants with retinal vein occlusion in the Study of Comparative Treatments for Retinal Vein Occlusion 2.MethodsSD-OCT scans of 362 participants were qualitatively assessed at baseline and months 1, 6, 12, and 24 for EZ status as normal, patchy, or absent. The thickness of EZ layer in the central subfield was also obtained using machine learning.ResultsEZ assessments were not possible at baseline due to signal blockage in >75% of eyes. At month 1, EZ was normal in 37.6%, patchy in 48.1%, and absent in 14.3%. EZ was measurable in 48.7% with a mean area of 0.07 ± 0.16 mm2. Mean VALS was better in eyes without an EZ defect compared to eyes with an EZ defect (P < 0.0001 at all visits). EZ defect at month 1 was associated with poorer VALS at all follow-up visits (P < 0.0001).ConclusionsBoth qualitative and quantitative assessments of EZ status strongly correlated with VALS. Absence of EZ was associated with poorer VALS at both corresponding and future visits, with larger areas of EZ loss associated with worse VALS.Translational relevanceAssessment of EZ can be used to identify patients with potentially poor response in eyes with retinal vein occlusion.
| S-EPMC7998009 | biostudies-literature
Project description:Most patients needing diabetic tractional retinal detachment (TRD) surgery are working-age adults that drive and participate in other vision-dependent activities of daily living. We sought to determine the proportion of patients that achieve functional visual acuity (VA) based on the World Health Organization (WHO) definition of 'low vision' (≤ 20/80) and US driving standards (≥ 20/40) after vitrectomy for diabetic TRD. In this 10-year retrospective review, consecutive patients who underwent primary vitrectomy for TRD from proliferative diabetic retinopathy were studied. 240 eyes in 203 patients met criteria for analysis (38 eyes were lost to follow up at 3 months; 68 at 12 months; 146 at 60 months). While most patients (nearly 80%) having TRD surgery had low vision pre-op, almost half attained VA that was > 20/80 five years post-op. Those most likely to achieve significant visual improvement (p < 0.0001) had concomitant vitreous hemorrhage pre-op. Only 6% of eyes met the US minimum driving standard before surgery based on VA compared to 28% after vitrectomy however this study did not examine visual fields which could warrant additional assessment depending on local requirements. In summary, significant gains in visual acuity are seen after vitrectomy for diabetic TRD that can result in functional improvement in activities of daily living.
| S-EPMC7519031 | biostudies-literature
Project description:PurposeTo investigate the effects of internal limiting membrane (ILM) peeling on visual acuity (VA) after rhegmatogenous retinal detachment (RRD) surgery.MethodsThis retrospective analysis examined the medical records of patients with RRD who underwent vitrectomy at 26 institutions. To detect prognostic factors of VA at 6 months postoperatively (post-VA), multivariate linear regression was performed with post-VA as the objective variable; ILM peeling, sex, age, preoperative VA (pre-VA), intraocular pressure, axial length, duration of RRD, and cataract surgery served as explanatory variables. Recurrence of RRD and epiretinal membrane formation within 6 months postoperatively were compared between groups of patients with and without ILM peeling, among patients with macula-on and macula-off RRD.ResultsThe inclusion criteria were met by 523 eyes with a macula-on RRD and 364 eyes with a macula-off RRD. ILM peeling was performed in 85 eyes with a macula-on RRD and 57 eyes with a macula-off RRD. In eyes with a macula-on RRD, ILM peeling did not affect post-VA (p = 0.72). Vitrectomy without cataract surgery and poor pre-VA were significantly associated with poor post-VA (p = 0.01 and p < 0.001, respectively). In eyes with a macula-off RRD, ILM peeling, long duration of RRD, and poor pre-VA were significantly associated with poor post-VA (p = 0.037, p = 0.007, and p < 0.001, respectively). Recurrence of RRD and epiretinal membrane formation were similar between groups of patients with and without ILM peeling, among patients with macula-on and macula-off RRD. Retina sensitivity was not evaluated by microperimetry.ConclusionILM peeling did not affect post-VA in eyes with a macula-on RRD, whereas post-VA was worse in eyes with ILM peeling than in eyes without peeling, among eyes with a macula-off RRD.
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Project description:Amblyopia is a developmental disorder associated with abnormal visual experience during early childhood commonly arising from strabismus and/or anisometropia and leading to dysfunctions in visual cortex and to various visual deficits. The different forms of neuronal activity that are attenuated in amblyopia have been only partially characterized. In electrophysiological recordings of healthy human brain, the presentation of visual stimuli is associated with event-related activity and oscillatory responses. It has remained poorly understood whether these forms of activity are reduced in amblyopia and whether possible dysfunctions would arise from lower- or higher-order visual areas. We recorded neuronal activity with magnetoencephalography (MEG) from anisometropic amblyopic patients and control participants during two visual tasks presented separately for each eye and estimated neuronal activity from source-reconstructed MEG data. We investigated whether event-related and oscillatory responses would be reduced for amblyopia and localized their cortical sources. Oscillation amplitudes and evoked responses were reduced for stimuli presented to the amblyopic eye in higher-order visual areas and in parietal and prefrontal cortices. Importantly, the reduction of oscillation amplitudes but not that of evoked responses was correlated with decreased visual acuity in amblyopia. These results show that attenuated oscillatory responses are correlated with visual deficits in anisometric amblyopia.
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