Repeated nuclear translocations underlie photoreceptor positioning and lamination of the outer nuclear layer in the mammalian retina

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.

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

Scientific Reports ◽

10.1038/s41598-021-90955-4 ◽

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.

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

European Journal of Ophthalmology ◽

10.1177/11206721211029465 ◽

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.

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CERKL, a retinal dystrophy gene, regulates mitochondrial function and dynamics in the mammalian retina

Neurobiology of Disease ◽

10.1016/j.nbd.2021.105405 ◽

2021 ◽

pp. 105405

Author(s):

Serena Mirra ◽

Rocío García Arroyo ◽

Elena B. Domènech ◽

Aleix Gavaldà-Navarro ◽

Carlos Herrera-Úbeda ◽

...

Keyword(s):

Mitochondrial Function ◽

Retinal Dystrophy ◽

Mammalian Retina

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

Scientific Reports ◽

10.1038/s41598-021-82107-5 ◽

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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Pathogenic STX3 variants affecting the retinal and intestinal transcripts cause an early-onset severe retinal dystrophy in microvillus inclusion disease subjects

Human Genetics ◽

10.1007/s00439-021-02284-1 ◽

2021 ◽

Author(s):

Andreas R. Janecke ◽

Xiaoqin Liu ◽

Rüdiger Adam ◽

Sumanth Punuru ◽

Arne Viestenz ◽

...

Keyword(s):

Early Onset ◽

Single Nucleotide Polymorphism Array ◽

Outer Nuclear Layer ◽

Retinal Dystrophy ◽

Geographic Origin ◽

Retinal Disease ◽

Homozygosity Mapping ◽

Rod Photoreceptor ◽

Loss Of Function ◽

Knockout Mouse Model

AbstractBiallelic STX3 variants were previously reported in five individuals with the severe congenital enteropathy, microvillus inclusion disease (MVID). Here, we provide a significant extension of the phenotypic spectrum caused by STX3 variants. We report ten individuals of diverse geographic origin with biallelic STX3 loss-of-function variants, identified through exome sequencing, single-nucleotide polymorphism array-based homozygosity mapping, and international collaboration. The evaluated individuals all presented with MVID. Eight individuals also displayed early-onset severe retinal dystrophy, i.e., syndromic—intestinal and retinal—disease. These individuals harbored STX3 variants that affected both the retinal and intestinal STX3 transcripts, whereas STX3 variants affected only the intestinal transcript in individuals with solitary MVID. That STX3 is essential for retinal photoreceptor survival was confirmed by the creation of a rod photoreceptor-specific STX3 knockout mouse model which revealed a time-dependent reduction in the number of rod photoreceptors, thinning of the outer nuclear layer, and the eventual loss of both rod and cone photoreceptors. Together, our results provide a link between STX3 loss-of-function variants and a human retinal dystrophy. Depending on the genomic site of a human loss-of-function STX3 variant, it can cause MVID, the novel intestinal-retinal syndrome reported here or, hypothetically, an isolated retinal dystrophy.

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