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Current Opinion in Neurobiology Aug 2023Understanding the formation of the complex nervous system hinges on decoding the mechanism that specifies a vast array of neuronal types, each endowed with a unique... (Review)
Review
Understanding the formation of the complex nervous system hinges on decoding the mechanism that specifies a vast array of neuronal types, each endowed with a unique morphology, physiology, and connectivity. As a pivotal step towards addressing this problem, seminal work has been devoted to characterizing distinct neuronal types. In recent years, high-throughput, single-cell transcriptomic methods have enabled a rapid inventory of cell types in various regions of the nervous system, with the retina exhibiting complete molecular characterization across many vertebrate species. This invaluable resource has furnished a fresh perspective for investigating the molecular principles of cell-type specification, thereby advancing our understanding of retinal development. Accordingly, this review focuses on the most recent transcriptomic characterizations of retinal cells, with a particular focus on amacrine cells and retinal ganglion cells. These investigations have unearthed new insights into their cell-type specification.
Topics: Transcriptome; Retina; Retinal Ganglion Cells; Amacrine Cells; Gene Expression Profiling
PubMed: 37499619
DOI: 10.1016/j.conb.2023.102752 -
Journal of Translational Medicine Mar 2024In diabetic retinopathy (DR), hypoxia-inducible factor (HIF-1α) induces oxidative stress by upregulating glycolysis. This process leads to neurodegeneration,...
BACKGROUND
In diabetic retinopathy (DR), hypoxia-inducible factor (HIF-1α) induces oxidative stress by upregulating glycolysis. This process leads to neurodegeneration, particularly photoreceptor cell damage, which further contributes to retinal microvascular deterioration. Further, the regulation of Wnt-inhibitory factor 1 (WIF1), a secreted Wnt signaling antagonist, has not been fully characterized in neurodegenerative eye diseases. We aimed to explore the impact of WIF1 on photoreceptor function within the context of DR.
METHOD
Twelve-week-old C57BL/KsJ-db/db mice were intravitreally injected with WIF1 overexpression lentivirus. After 4 weeks, optical coherence tomography (OCT), transmission electron microscopy (TEM), H&E staining, and electroretinography (ERG) were used to assess the retinal tissue and function. The potential mechanism of action of WIF1 in photoreceptor cells was explored using single-cell RNA sequencing. Under high-glucose conditions, 661 W cells were used as an in vitro DR model. WIF1-mediated signaling pathway components were assessed using quantitative real-time PCR, immunostaining, and western blotting.
RESULT
Typical diabetic manifestations were observed in db/db mice. Notably, the expression of WIF1 was decreased at the mRNA and protein levels. These pathological manifestations and visual function improved after WIF1 overexpression in db/db mice. TEM demonstrated that WIF1 restored damaged mitochondria, the Golgi apparatus, and photoreceptor outer segments. Moreover, ERG indicated the recovery of a-wave potential amplitude. Single-cell RNA sequencing and in vitro experiments suggested that WIF1 overexpression prevented the expression of glycolytic enzymes and lactate production by inhibiting the canonical Wnt signaling pathway, HIF-1α, and Glut1, thereby reducing retinal and cellular reactive oxygen species levels and maintaining 661 W cell viability.
CONCLUSIONS
WIF1 exerts an inhibitory effect on the Wnt/β-catenin-HIF-1α-Glut1 glycolytic pathway, thereby alleviating oxidative stress levels and mitigating pathological structural characteristics in retinal photoreceptor cells. This mechanism helps preserve the function of photoreceptor cells in DR and indicates that WIF1 holds promise as a potential therapeutic candidate for DR and other neurodegenerative ocular disorders.
Topics: Animals; Mice; Diabetes Mellitus; Diabetic Retinopathy; Glucose Transporter Type 1; Mice, Inbred C57BL; Photoreceptor Cells; Retina
PubMed: 38448948
DOI: 10.1186/s12967-024-05046-5 -
Investigative Ophthalmology & Visual... Mar 2024To investigate topographical maps of the three-dimensional choroidal vascularity index (3D-CVI) in children with different levels of myopia.
PURPOSE
To investigate topographical maps of the three-dimensional choroidal vascularity index (3D-CVI) in children with different levels of myopia.
METHODS
We enrolled 274 eyes from 143 children with various severity of myopia, including emmetropia (EM), low myopia (LM), and moderate-high myopia (MHM). The choroidal vessel volume (CVV), choroidal stroma volume (CSV), and 3D-CVI in different eccentricities (fovea, parafovea, and perifovea) and quadrants (nasal, temporal, superior, and inferior) were obtained from swept-source optical coherence tomography angiography (SS-OCTA) volume scans. All choroidal parameters were compared among groups, and the associated factors contributing to different 3D-CVIs were analyzed.
RESULTS
Compared to the less myopic group, the more myopic group showed a significant decrease in CVV and CSV (MHM < LM < EM) and a significant increase in the 3D-CVI (MHM > LM > EM) in most areas (all P < 0.05). The nasal quadrant had the greatest 3D-CVI and lowest CSV and CVV, and vice versa in the temporal quadrant. The 3D-CVIs of the EM and LM groups gradually increased from the fovea to the perifovea, whereas the 3D-CVI of the MHM group first decreased and then increased. Regression analysis showed that axial length was an independent risk factor affecting foveal and parafoveal 3D-CVIs. Restricted cubic spline analysis revealed that the 3D-CVI increased with spherical equivalent (SE) when the SE was less than threshold and decreased when the SE was greater than threshold (SE thresholds for foveal, parafoveal, and perifoveal 3D-CVIs were -5.25 D, -5.125 D, and -2.00 D, respectively; all P < 0.05).
CONCLUSIONS
Children with myopia exhibited decreased CSV and CVV, increased 3D-CVIs, and altered 3D-CVI eccentricity characteristics (from the fovea to the perifovea). The quadratic relationship between the 3D-CVI and SE should be explored in longitudinal investigations.
Topics: Child; Humans; Myopia; Choroid; Brain Diseases; Fovea Centralis; Refraction, Ocular
PubMed: 38466287
DOI: 10.1167/iovs.65.3.14 -
The British Journal of Ophthalmology May 2024To investigate myopic maculopathy in Chinese children with high myopia and its association with choroidal and retinal changes.
AIMS
To investigate myopic maculopathy in Chinese children with high myopia and its association with choroidal and retinal changes.
METHODS
This cross-sectional study included Chinese children aged 4-18 years with high myopia. Myopic maculopathy was classified by fundus photography and retinal thickness (RT) and choroidal thickness (ChT) in the posterior pole were measured by swept-source optical coherence tomography. A receiver operation curve was used to determine the efficacy of fundus factors in classifying myopic maculopathy.
RESULTS
In total, 579 children aged 12.8±3.2 years with a mean spherical equivalent of -8.44±2.20 D were included. The proportions of tessellated fundus and diffuse chorioretinal atrophy were 43.52% (N=252) and 8.64% (N=50), respectively. Tessellated fundus was associated with a thinner macular ChT (OR=0.968, 95% CI: 0.961 to 0.975, p<0.001) and RT (OR=0.977, 95% CI: 0.959 to 0.996, p=0.016), longer axial length (OR=1.545, 95% CI: 1.198 to 1.991, p=0.001) and older age (OR=1.134, 95% CI: 1.047 to 1.228, p=0.002) and less associated with male children (OR=0.564, 95% CI: 0.348 to 0.914, p=0.020). Only a thinner macular ChT (OR=0.942, 95% CI: 0.926 to 0.959, p<0.001) was independently associated with diffuse chorioretinal atrophy. When using nasal macular ChT for classifying myopic maculopathy, the optimal cut-off value was 129.00 µm (area under the curve (AUC)=0.801) and 83.85 µm (AUC=0.910) for tessellated fundus and diffuse chorioretinal atrophy, respectively.
CONCLUSION
A large proportion of highly myopic Chinese children suffer from myopic maculopathy. Nasal macular ChT may serve as a useful index for classifying and assessing paediatric myopic maculopathy.
TRIAL REGISTRATION NUMBER
NCT03666052.
Topics: Humans; Child; Male; Cross-Sectional Studies; Female; Tomography, Optical Coherence; Adolescent; Child, Preschool; Myopia, Degenerative; Choroid; China; Retina; Visual Acuity; Retinal Diseases; Asian People; ROC Curve; East Asian People
PubMed: 37290823
DOI: 10.1136/bjo-2022-321839 -
Translational Vision Science &... Jul 2023Morphological changes to the optic nerve head (ONH) can be detected at the early stages of glaucoma. Three-dimensional imaging and analysis may aid in the diagnosis....
PURPOSE
Morphological changes to the optic nerve head (ONH) can be detected at the early stages of glaucoma. Three-dimensional imaging and analysis may aid in the diagnosis. Light field (LF) fundus cameras can generate three-dimensional (3D) images of optic disc topography from a single shot and are less susceptible to motion artifacts. Here, we introduce a processing method to determine diagnostically relevant ONH parameters automatically and present the results of a subject study performed to validate this method.
METHODS
The ONHs of 17 healthy subjects were examined and images were acquired with both an LF fundus camera and by optical coherence tomography (OCT). The LF data were analyzed with a novel algorithm and compared with the results of the OCT study. Depth information was reconstructed, and a model with radial basis functions was used for processing of the 3D point cloud and to provide a finite surface. The peripapillary rising and falling edges were evaluated to determine optic disc and cup contours and finally calculate the parameters.
RESULTS
Nine of the 17 subjects exhibited prominent optic cups. The contours and ONH parameters determined by an analysis of LF 3D imaging largely agreed with the data obtained from OCT. The median disc areas, cup areas, and cup depths differed by 0.17 mm², -0.04 mm², and -0.07 mm, respectively.
CONCLUSIONS
The findings presented here suggest the possibility of using LF data to evaluate the ONH.
TRANSLATIONAL RELEVANCE
LF data can be used to determine geometric parameters of the ONH and thus may be suitable for future use in glaucoma diagnostics.
Topics: Humans; Optic Disk; Fundus Oculi; Glaucoma; Algorithms; Healthy Volunteers
PubMed: 37490305
DOI: 10.1167/tvst.12.7.21 -
BMJ Open Ophthalmology Oct 2023To investigate associations between baseline macular pigment optical density (MPOD) and retinal layer thicknesses in eyes with and without manifest primary open-angle...
OBJECTIVE
To investigate associations between baseline macular pigment optical density (MPOD) and retinal layer thicknesses in eyes with and without manifest primary open-angle glaucoma (POAG) in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2).
METHODS AND ANALYSIS
MPOD was measured at CAREDS baseline (2001-2004) via heterochromatic flicker photometry (0.5° from foveal centre). Peripapillary retinal nerve fibre layer (RNFL), macular ganglion cell complex (GCC), ganglion cell layer (GCL), inner plexiform layer (IPL), and RNFL thicknesses were measured at CAREDS2 (2016-2019) via spectral-domain optical coherence tomography. Associations between MPOD and retinal thickness were assessed using multivariable linear regression.
RESULTS
Among 742 eyes (379 participants), manifest POAG was identified in 50 eyes (32 participants). In eyes without manifest POAG, MPOD was positively associated with macular GCC, GCL and IPL thicknesses in the central subfield (P-trend ≤0.01), but not the inner or outer subfields. Among eyes with manifest POAG, MPOD was positively associated with macular GCC, GCL, IPL and RNFL in the central subfield (P-trend ≤0.03), but not the inner or outer subfields, and was positively associated with peripapillary RNFL thickness in the superior and temporal quadrants (P-trend≤0.006).
CONCLUSION
We observed a positive association between MPOD and central subfield GCC thickness 15 years later. MPOD was positively associated with peripapillary RNFL superior and temporal quadrant thicknesses among eyes with manifest POAG. Our results linking low MPOD to retinal layers that are structural indicators of early glaucoma provide further evidence that carotenoids may be protective against manifest POAG.
Topics: Humans; Macular Pigment; Glaucoma, Open-Angle; Macula Lutea; Retinal Ganglion Cells; Intraocular Pressure; Tomography, Optical Coherence
PubMed: 37890895
DOI: 10.1136/bmjophth-2023-001331 -
Indian Journal of Ophthalmology Oct 2023To evaluate retinal and choroidal alterations in eyes with inactive ocular sarcoidosis and to compare the findings with healthy controls.
PURPOSE
To evaluate retinal and choroidal alterations in eyes with inactive ocular sarcoidosis and to compare the findings with healthy controls.
METHODS
This cross-sectional study included 11 patients with inactive ocular sarcoidosis (study group) and 11 healthy individuals (control group). Retinal and choroidal vascular differences were evaluated using optical coherence tomography angiography (OCTA) and enhanced depth imaging-optical coherence tomography (EDI-OCT).
RESULTS
A total of 21 eyes of ocular sarcoidosis patients without active inflammation and 22 eyes of healthy controls were analyzed. The mean whole-image deep capillary plexus vessel density was significantly lower in the study group than in the control group (P = 0.03). The acircularity index values were significantly higher, and the foveal density-300 values were significantly lower in the study group than in the control group (P = 0.01, both). The flow areas of the choriocapillaris at 1-, 2-, and 3-mm radius areas were also significantly lower in the study group (all P < 0.01). The mean choroidal thickness (CT) was significantly lower in all regions between nasal and temporal at 3000 μm in the study group (all P < 0.05). The choroidal vascularity index (CVI) values were also significantly lower in the study group (P < 0.01).
CONCLUSION
Ocular sarcoidosis was associated with a reduction in CT and the CVI with a decrease in retinal vessel density and choriocapillary flow parameters. The combination of OCTA and EDI-OCT imaging may be useful in monitoring ocular sarcoidosis eyes to detect alterations in the retinal and choroidal layers.
Topics: Humans; Microcirculation; Cross-Sectional Studies; Retina; Choroid; Sarcoidosis; Endophthalmitis
PubMed: 37787237
DOI: 10.4103/IJO.IJO_3262_22 -
Investigative Ophthalmology & Visual... Jan 2024To compare optical coherence tomography angiography (OCTA) retina metrics between cognitively healthy subjects with pathological versus normal cerebrospinal fluid (CSF)... (Comparative Study)
Comparative Study
PURPOSE
To compare optical coherence tomography angiography (OCTA) retina metrics between cognitively healthy subjects with pathological versus normal cerebrospinal fluid (CSF) Aβ42/tau ratios.
METHODS
Swept-source OCTA scans were collected using the Zeiss PLEX Elite 9000 and analyzed on 23 cognitively healthy (CH) subjects who had previously undergone CSF analysis. Thirteen subjects had a pathological Aβ42/tau (PAT) ratio of <2.7132, indicative of presymptomatic Alzheimer's disease (AD), and 10 had a normal Aβ42/tau (NAT) ratio of ≥2.7132. OCTA en face images of the superficial vascular complex (SVC) and deep vascular complex were binarized and skeletonized to quantify the perfusion density (PD), vessel length density (VLD), and fractal dimension (FrD). The foveal avascular zone (FAZ) area was calculated using the SVC slab. Choriocapillaris flow deficits (CCFDs) were computed from the en face OCTA slab of the CC. The above parameters were compared between CH-PATs and CH-NATs.
RESULTS
Compared to CH-NATs, CH-PATs showed significantly decreased PD, VLD, and FrD in the SVC, with a significantly increased FAZ area and CCFDs.
CONCLUSIONS
Swept-source OCTA analysis of the SVC and CC suggests a significant vascular loss at the CH stage of pre-AD that might be an indicator of a neurodegenerative process initiated by the impaired clearance of Aβ42 in the blood vessel wall and by phosphorylated tau accumulation in the perivascular spaces, a process that most likely mirrors that in the brain. If confirmed in larger longitudinal studies, OCTA retinal and inner choroidal metrics may be important biomarkers for assessing presymptomatic AD.
Topics: Humans; Alzheimer Disease; Angiography; Choroid; Macula Lutea; Retina; Tomography, Optical Coherence; Cerebrospinal Fluid; Amyloidogenic Proteins; Neurodegenerative Diseases
PubMed: 38294804
DOI: 10.1167/iovs.65.1.47 -
Nature Communications Aug 2023In vertebrate vision, early retinal circuits divide incoming visual information into functionally opposite elementary signals: On and Off, transient and sustained,...
In vertebrate vision, early retinal circuits divide incoming visual information into functionally opposite elementary signals: On and Off, transient and sustained, chromatic and achromatic. Together these signals can yield an efficient representation of the scene for transmission to the brain via the optic nerve. However, this long-standing interpretation of retinal function is based on mammals, and it is unclear whether this functional arrangement is common to all vertebrates. Here we show that male poultry chicks use a fundamentally different strategy to communicate information from the eye to the brain. Rather than using functionally opposite pairs of retinal output channels, chicks encode the polarity, timing, and spectral composition of visual stimuli in a highly correlated manner: fast achromatic information is encoded by Off-circuits, and slow chromatic information overwhelmingly by On-circuits. Moreover, most retinal output channels combine On- and Off-circuits to simultaneously encode, or multiplex, both achromatic and chromatic information. Our results from birds conform to evidence from fish, amphibians, and reptiles which retain the full ancestral complement of four spectral types of cone photoreceptors.
Topics: Male; Animals; Retina; Chickens; Retinal Cone Photoreceptor Cells; Brain; Excipients; Mammals
PubMed: 37652912
DOI: 10.1038/s41467-023-41032-z -
Scientific Reports Aug 2023Macular edema (ME), the accumulation of intraretinal fluid in the macula, is a common sight affecting sequelae of retinitis pigmentosa (RP). However, it is unclear why...
Macular edema (ME), the accumulation of intraretinal fluid in the macula, is a common sight affecting sequelae of retinitis pigmentosa (RP). However, it is unclear why some patients develop ME, and others do not. This study aims to identify associations between clinical-genetic factors in RP with ME. Patients with clinically confirmed RP cases were identified from the inherited retinal disease database at a large tertiary referral academic center. Demographic and genetic testing findings were noted. Additionally, optical coherence tomography volume scans were graded using a validated grading system. One hundred and six patients (73.1%) were found to have ME in at least one eye (OD = 88, mean = 37.9%, OS = 98, mean = 31.7%). Structurally, the presence of epiretinal membrane (ERM) (p < 0.007) and vitreo-macular traction (VMT) (p < 0.003) were significantly associated with ME. Additionally, X-linked (p < 0.032) and autosomal dominant inheritance (p < 0.039) demonstrated a significant association with ME, with RP1 (p < 0.045) and EYS (p < 0.017) pathogenic variants also significantly associated with ME. This study, in a large cohort of RP patients, confirms previous retinal structural associations for ME in RP and identifies potential new genetic associations.
Topics: Humans; Macular Edema; Retinitis Pigmentosa; Retina; Retinal Diseases; Macula Lutea; Eye Proteins
PubMed: 37648803
DOI: 10.1038/s41598-023-41464-z