scholarly journals Retinal Development and Pathophysiology in Kcnj13 Knockout Mice

2022 ◽  
Vol 9 ◽  
Author(s):  
Xiaodong Jiao ◽  
Zhiwei Ma ◽  
Jingqi Lei ◽  
Pinghu Liu ◽  
Xiaoyu Cai ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Knockout Mice ◽  
Ciliary Body ◽  
Outer Nuclear Layer ◽  
Plexiform Layer ◽  
Bipolar Cells ◽  
Conditional Knockout ◽  
Intron 1 ◽  
Vitreoretinal Degeneration ◽  
Inwardly Rectifying

Purpose: We constructed and characterized knockout and conditional knockout mice for KCNJ13, encoding the inwardly rectifying K+ channel of the Kir superfamily Kir7.1, mutations in which cause both Snowflake Vitreoretinal Degeneration (SVD) and Retinitis pigmentosa (RP) to further elucidate the pathology of this disease and to develop a potential model system for gene therapy trials.Methods: A Kcnj13 knockout mouse line was constructed by inserting a gene trap cassette expressing beta-galactosidase flanked by FRT sites in intron 1 with LoxP sites flanking exon two and converted to a conditional knockout by FLP recombination followed by crossing with C57BL/6J mice having Cre driven by the VMD2 promoter. Lentiviral replacement of Kcnj13 was driven by the EF1a or VMD2 promoters.Results: Blue-Gal expression is evident in E12.5 brain ventricular choroid plexus, lens, neural retina layer, and anterior RPE. In the adult eye expression is seen in the ciliary body, RPE and choroid. Adult conditional Kcnj13 ko mice show loss of photoreceptors in the outer nuclear layer, inner nuclear layer thinning with loss of bipolar cells, and thinning and disruption of the outer plexiform layer, correlating with Cre expression in the overlying RPE which, although preserved, shows morphological disruption. Fundoscopy and OCT show signs of retinal degeneration consistent with the histology, and photopic and scotopic ERGs are decreased in amplitude or extinguished. Lentiviral based replacement of Kcnj13 resulted in increased ERG c- but not a- or b- wave amplitudes.Conclusion: Ocular KCNJ13 expression starts in the choroid, lens, ciliary body, and anterior retina, while later expression centers on the RPE with no/lower expression in the neuroretina. Although KCNJ13 expression is not required for survival of the RPE, it is necessary for RPE maintenance of the photoreceptors, and loss of the photoreceptor, outer plexiform, and outer nuclear layers occur in adult KCNJ13 cKO mice, concomitant with decreased amplitude and eventual extinguishing of the ERG and signs of retinitis pigmentosa on fundoscopy and OCT. Kcnj13 replacement resulting in recovery of the ERG c- but not a- and b-waves is consistent with the degree of photoreceptor degeneration seen on histology.

scholarly journals Thenob2mouse, a null mutation inCacna1f: Anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses

2006 ◽  
Vol 23 (1) ◽  
pp. 11-24 ◽  
Author(s):  
BO CHANG ◽  
JOHN R. HECKENLIVELY ◽  
PHILIPPA R. BAYLEY ◽  
NICHOLAS C. BRECHA ◽  
MURIEL T. DAVISSON ◽  
...  
Keyword(s):  
Visual Information ◽  
Synapse Formation ◽  
Dynamic Range ◽  
Outer Nuclear Layer ◽  
Glutamate Release ◽  
Plexiform Layer ◽  
Bipolar Cells ◽  
Null Mutation ◽  
Visual Responses

Glutamate release from photoreceptor terminals is controlled by voltage-dependent calcium channels (VDCCs). In humans, mutations in theCacna1fgene, encoding the α1Fsubunit of VDCCs, underlie the incomplete form of X-linked congenital stationary night blindness (CSNB2). These mutations impair synaptic transmission from rod and cone photoreceptors to bipolar cells. Here, we report anatomical and functional characterizations of the retina in thenob2(no b-wave 2) mouse, a naturally occurring mutant caused by a null mutation inCacna1f. Not surprisingly, theb-waves of both the light- and dark-adapted electroretinogram are abnormal innob2mice. The outer plexiform layer (OPL) is disorganized, with extension of ectopic neurites through the outer nuclear layer that originate from rod bipolar and horizontal cells, but not from hyperpolarizing bipolar cells. These ectopic neurites continue to express mGluR6, which is frequently associated with profiles that label with the presynaptic marker Ribeye, indicating potential points of ectopic synapse formation. However, the morphology of the presynaptic Ribeye-positive profiles is abnormal. While cone pedicles are present their morphology also appears compromised. Characterizations of visual responses in retinal ganglion cellsin vivo, under photopic conditions, demonstrate that ON-center cells have a reduced dynamic range, although their basic center-surround organization is retained; no alteration in the responses of OFF-center cells was evident. These results indicate thatnob2mice are a valuable model in which to explore the pathophysiological mechanisms associated withCacna1fmutations causing CSNB2, and the subsequent effects on visual information processing. Further, thenob2mouse represents a model system in which to define the signals that guide synapse formation and/or maintenance in the OPL.

scholarly journals Bistratified starburst amacrine cells in Sox2 conditional knockout mouse retina display ON and OFF responses

2018 ◽  
Vol 120 (4) ◽  
pp. 2121-2129 ◽  
Author(s):  
Todd L. Stincic ◽  
Patrick W. Keeley ◽  
Benjamin E. Reese ◽  
W. Rowland Taylor
Keyword(s):  
Transcription Factor ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Conditional Knockout ◽  
Physiological Data ◽  
Mouse Retina ◽  
Inner Plexiform Layer ◽  
Environmental Signals ◽  
Starburst Amacrine Cells

Cell-intrinsic factors, in conjunction with environmental signals, guide migration, differentiation, and connectivity during early development of neuronal circuits. Within the retina, inhibitory starburst amacrine cells (SBACs) comprise ON types with somas in the ganglion cell layer (GCL) and dendrites stratifying narrowly in the inner half of the inner plexiform layer (IPL) and OFF types with somas in the inner nuclear layer (INL) and dendrites stratifying narrowly in the outer half of the IPL. The transcription factor Sox2 is crucial to this subtype specification. Without Sox2, many ON-type SBACs destined for the GCL settle in the INL while many that reach the GCL develop bistratified dendritic arbors. This study asked whether ON-type SBACs in Sox2-conditional knockout retinas exhibit selective connectivity only with ON-type bipolar cells or their bistratified morphology allows them to connect to both ON and OFF bipolar cells. Physiological data demonstrate that these cells receive ON and OFF excitatory inputs, indicating that the ectopically stratified dendrites make functional synapses with bipolar cells. The excitatory inputs were smaller and more transient in Sox2-conditional knockout compared with wild type; however, inhibitory inputs appeared largely unchanged. Thus dendritic stratification, rather than cellular identification, may be the major factor that determines ON vs. OFF connectivity. NEW & NOTEWORTHY Conditional knockout of the transcription factor Sox2 during early embryogenesis converts a monostratifying starburst amacrine cell into a bistratifying starburst cell. Here we show that these bistratifying starburst amacrine cells form functional synaptic connections with both ON and OFF bipolar cells. This suggests that normal ON vs. OFF starburst connectivity may not require distinct molecular specification. Proximity alone may be sufficient to allow formation of functional synapses.

Ankyrin-G heterozygous conditional knockout mice display increased sensitivity to social defeat stress

2021 ◽  
Author(s):  
Zachary A. Cordner ◽  
Seva G. Khambadkone ◽  
Shanshan Zhu ◽  
Justin Bai ◽  
Rasadokht Forati ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Social Defeat ◽  
Conditional Knockout ◽  
Social Defeat Stress ◽  
Conditional Knockout Mice ◽  
Ankyrin G ◽  
Increased Sensitivity

scholarly journals En face image-based classification of diabetic macular edema using swept source optical coherence tomography

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Atsushi Fujiwara ◽  
Yuki Kanzaki ◽  
Shuhei Kimura ◽  
Mio Hosokawa ◽  
Yusuke Shiode ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Outer Nuclear Layer ◽  
Subretinal Fluid ◽  
Plexiform Layer ◽  
Optical Coherence ◽  
Fiber Layer ◽  
Swept Source ◽  
En Face

AbstractThis retrospective study was performed to classify diabetic macular edema (DME) based on the localization and area of the fluid and to investigate the relationship of the classification with visual acuity (VA). The fluid was visualized using en face optical coherence tomography (OCT) images constructed using swept-source OCT. A total of 128 eyes with DME were included. The retina was segmented into: Segment 1, mainly comprising the inner nuclear layer and outer plexiform layer, including Henle’s fiber layer; and Segment 2, mainly comprising the outer nuclear layer. DME was classified as: foveal cystoid space at Segment 1 and no fluid at Segment 2 (n = 24), parafoveal cystoid space at Segment 1 and no fluid at Segment 2 (n = 25), parafoveal cystoid space at Segment 1 and diffuse fluid at Segment 2 (n = 16), diffuse fluid at both segments (n = 37), and diffuse fluid at both segments with subretinal fluid (n = 26). Eyes with diffuse fluid at Segment 2 showed significantly poorer VA, higher ellipsoid zone disruption rates, and greater central subfield thickness than did those without fluid at Segment 2 (P < 0.001 for all). These results indicate the importance of the localization and area of the fluid for VA in DME.

Reduced hippocampal ten-eleven translocation 3 (Tet3) protein expression in Tet3 conditional knockout mice

2021 ◽  
Vol 26 (5) ◽  
pp. 1425-1425
Author(s):  
Cláudia Antunes ◽  
Jorge D. Da Silva ◽  
Sónia Guerra-Gomes ◽  
Nuno D. Alves ◽  
Fábio Ferreira ◽  
...  
Keyword(s):  
Protein Expression ◽  
Knockout Mice ◽  
Conditional Knockout ◽  
Conditional Knockout Mice

scholarly journals Changes in each retinal layer and ellipsoid zone recovery after full-thickness macular hole surgery

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Min-Woo Lee ◽  
Tae-Yeon Kim ◽  
Yong-Yeon Song ◽  
Seung-Kook Baek ◽  
Young-Hoon Lee
Keyword(s):  
Macular Hole ◽  
Axial Length ◽  
Outer Nuclear Layer ◽  
Plexiform Layer ◽  
Retinal Layer ◽  
Inner Plexiform Layer ◽  
Full Thickness ◽  
Ellipsoid Zone ◽  
Full Thickness Macular Hole ◽  
Fellow Eyes

AbstractTo analyze the changes in each retinal layer and the recovery of the ellipsoid zone (EZ) after full-thickness macular hole (FTMH) surgery. Patients who underwent surgery for FTMH were included. Spectral-domain optical coherence tomography (SD-OCT) was performed preoperatively and postoperatively at 1, 3, 6, 9, and 12 months. A total of 32 eyes were enrolled. Ganglion cell layer, inner plexiform layer, and inner nuclear layer showed significant reductions over time after surgery (P = 0.020, P = 0.001, and P = 0.001, respectively), but were significantly thicker than those of fellow eyes at 12 months postoperatively. The average recovery duration of the external limiting membrane (ELM), outer nuclear layer (ONL), and EZ was 1.5, 2.1, and 6.1 months, respectively. Baseline best-corrected visual acuity (BCVA) (P = 0.003), minimum linear diameter (MLD) (P = 0.025), recovery of EZ (P = 0.008), and IRL thickness (P < 0.001) were significant factors associated with changes in the BCVA. Additionally, axial length (P < 0.001), MLD (P = 0.020), and IRL thickness (P = 0.001) showed significant results associated with EZ recovery. The IRL gradually became thinner after FTMH surgery but was still thicker than that of the fellow eye at 12 months postoperatively. The recovery of ELM and ONL may be a prerequisite for the EZ recovery. The BCVA change was affected by baseline BCVA, MLD, recovery of EZ, and IRL thickness. Additionally, axial length, MLD, and IRL thickness were significantly associated with EZ recovery.

Evaluation of retinal inflammatory biomarkers after intravitreal steroid implant and Ranibizumab injection in diabetic macular edema

2021 ◽  
pp. 112067212110294
Author(s):  
Ilkay Kilic Muftuoglu ◽  
Ecem Onder Tokuc ◽  
Fatma Sümer ◽  
V Levent Karabas
Keyword(s):  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Outer Nuclear Layer ◽  
Plexiform Layer ◽  
Retinal Layer ◽  
Treatment Naïve ◽  
The Mean ◽  
The Individual ◽  
Inflammatory Component

Purpose: To compare the efficacy of intravitreal (IV) ranibizumab (IVR) injection with IV dexamethasone implant (IVDEX) in treatment naive diabetic macular edema (DME) patients with inflammatory component. Materials and methods: Treatment naive DME eyes with subfoveal neurosensorial detachment (SND) and hyperreflective spots (HRS) were treated either three loading doses of IVR (18 eyes) or one dose of IVDEX (19 eyes). Central macular thickness (CMT), height of SND, the number of HRSs scattered on the individual retinal layers and photoreceptor integrity were assessed using spectral domain- optical coherence tomography scans over 3-months follow-up. Results: The mean change in best-corrected visual acuity (BCVA) was −0.11 ± 0.08 logMAR in IVDEX group and −0.04 ± 0.06 logMAR in IVR group at 1-month ( p = 0.011). IVDEX group showed statistically significant more increase in BCVA compared to those receiving IVR injections at 2-months ( p = 0.004) and 3-months ( p = 0.017) visits. Compared to baseline, the number of total HRSs and the number of HRSs at each individual inner retinal layer significantly decreased in both groups at all follow-up visits. However, IVDEX group showed more decrease in the total number of HRSs at 2- and 3-months ( p < 0.001 at 2-months, and p = 0.006 at 3-months) and in the mean number of HRSs located at inner nuclear layer–outer plexiform layer level ( p = 0.016 at 1-month, p < 0.001 at 2-months, and p < 0.001 at 3-months). After treatment, the number of HRSs on the outer nuclear layer showed some non-significant increase in both groups. Conclusion: HRSs tended to migrate from inner retina to the outer retina in DME eyes by treatment. Dexamethasone seemed to be more effective option in such cases with inflammatory component.

scholarly journals Inner and outer retinal layer thickness alterations in pediatric and juvenile craniopharyngioma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ga-In Lee ◽  
Kyung-Ah Park ◽  
Sei Yeul Oh ◽  
Doo-Sik Kong ◽  
Sang Duk Hong
Keyword(s):  
Layer Thickness ◽  
Outer Nuclear Layer ◽  
Plexiform Layer ◽  
Visual Field Defects ◽  
Retinal Layer ◽  
Inner Plexiform Layer ◽  
Healthy Controls ◽  
Fiber Layer ◽  
Photoreceptor Layer ◽  
Chiasmal Compression

AbstractWe evaluated postoperative retinal thickness in pediatric and juvenile craniopharyngioma (CP) patients with chiasmal compression using optical coherence tomography (OCT) auto-segmentation. We included 18 eyes of 18 pediatric or juvenile patients with CP and 20 healthy controls. Each thickness of the macular retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer, outer plexiform layer, outer nuclear layer, and photoreceptor layer was compared between the CP patients and healthy controls. There was significant thinning in the macular RNFL (estimates [μm], superior, − 10.68; inferior, − 7.24; nasal, − 14.22), all quadrants of GCL (superior, − 16.53; inferior, − 14.37; nasal, − 24.34; temporal, − 9.91) and IPL (superior, − 11.45; inferior, − 9.76; nasal, − 15.25; temporal, − 4.97) in pediatric and juvenile CP patients postoperatively compared to healthy control eyes after adjusting for age and refractive errors. Thickness reduction in the average and nasal quadrant of RNFL, GCL, and IPL was associated with peripapillary RNFL thickness, and reduced nasal quadrant GCL and IPL thicknesses were associated with postoperative visual field defects. In pediatric and juvenile patients with CP, decreased inner retinal layer thickness following chiasmal compression was observed. The changes in retinal structures were closely related to peripapillary RNFL thinning and functional outcomes.

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