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Bioelectronic Medicine Jun 2024Blue light activates melanopsin, a photopigment that is expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs). The axons of ipRGCs converge on the...
BACKGROUND
Blue light activates melanopsin, a photopigment that is expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs). The axons of ipRGCs converge on the optic disc, which corresponds to the physiological blind spot in the visual field. Thus, a blue light stimulus aligned with the blind spot captures the ipRGCs axons at the optic disc. This study examined the potential changes in choroidal thickness and axial length associated with blue light stimulation of melanopsin-expressing ipRGCs at the blind spot. It was hypothesized that blue light stimulation at the blind spot in adults increases choroidal thickness.
METHODS
The blind spots of both eyes of 10 emmetropes and 10 myopes, with a mean age of 28 ± 6 years (SD), were stimulated locally for 1-minute with blue flickering light with a 460 nm peak wavelength. Measurements of choroidal thickness and axial length were collected from the left eye before stimulation and over a 60-minute poststimulation period. At a similar time of day, choroidal thickness and axial length were measured under sham control condition in all participants, while a subset of 3 emmetropes and 3 myopes were measured after 1-minute of red flickering light stimulation of the blind spot with a peak wavelength of 620 nm. Linear mixed model analyses were performed to examine the light-induced changes in choroidal thickness and axial length over time and between refractive groups.
RESULTS
Compared with sham control (2 ± 1 μm, n = 20) and red light (-1 ± 2 μm, n = 6) stimulation, subfoveal choroidal thickness increased within 60 min after blue light stimulation of the blind spot (7 ± 1 μm, n = 20; main effect of light, p < 0.001). Significant choroidal thickening after blue light stimulation occurred in emmetropes (10 ± 2 μm, p < 0.001) but not in myopes (4 ± 2 μm, p > 0.05). Choroidal thickening after blue light stimulation was greater in the fovea, diminishing in the parafoveal and perifoveal regions. There was no significant main effect of light, or light by refractive error interaction on the axial length after blind spot stimulation.
CONCLUSIONS
These findings demonstrate that stimulating melanopsin-expressing axons of ipRGCs at the blind spot with blue light increases choroidal thickness in young adults. This has potential implications for regulating eye growth.
PubMed: 38825695
DOI: 10.1186/s42234-024-00146-5 -
Cell Reports Jun 2024Atoh7 is transiently expressed in retinal progenitor cells (RPCs) and is required for retinal ganglion cell (RGC) differentiation. In humans, a deletion in a distal...
Atoh7 is transiently expressed in retinal progenitor cells (RPCs) and is required for retinal ganglion cell (RGC) differentiation. In humans, a deletion in a distal non-coding regulatory region upstream of ATOH7 is associated with optic nerve atrophy and blindness. Here, we functionally interrogate the significance of the Atoh7 regulatory landscape to retinogenesis in mice. Deletion of the Atoh7 enhancer structure leads to RGC deficiency, optic nerve hypoplasia, and retinal blood vascular abnormalities, phenocopying inactivation of Atoh7. Further, loss of the Atoh7 remote enhancer impacts ipsilaterally projecting RGCs and disrupts proper axonal projections to the visual thalamus. Deletion of the Atoh7 remote enhancer is also associated with the dysregulation of axonogenesis genes, including the derepression of the axon repulsive cue Robo3. Our data provide insights into how Atoh7 enhancer elements function to promote RGC development and optic nerve formation and highlight a key role of Atoh7 in the transcriptional control of axon guidance molecules.
Topics: Animals; Retinal Ganglion Cells; Basic Helix-Loop-Helix Transcription Factors; Mice; Axons; Enhancer Elements, Genetic; Neurogenesis; Nerve Tissue Proteins; Receptors, Immunologic; Optic Nerve; Cell Differentiation; Gene Expression Regulation, Developmental; Retina; Mice, Inbred C57BL; Roundabout Proteins; Receptors, Cell Surface
PubMed: 38823017
DOI: 10.1016/j.celrep.2024.114291 -
Ophthalmology and Therapy Jul 2024This study investigates how surgery for pituitary adenoma (PA) affects the visual pathway, examining changes in the retina, blood vessel density, and nerve function....
INTRODUCTION
This study investigates how surgery for pituitary adenoma (PA) affects the visual pathway, examining changes in the retina, blood vessel density, and nerve function. Since PAs often impair vision as a result of their location near visual structures, this research is key to understanding and improving vision recovery after surgery.
METHODS
Our study is based on a retrospective analysis of the historical data of 28 patients diagnosed with pituitary adenomas. We conducted assessments by reviewing preoperative and postoperative imaging records. These included optical coherence tomography (OCT) for retinal structure analysis, diffusion tensor imaging (DTI) for neural transmission evaluation, and optical coherence tomography angiography for assessing blood vessel density. These tools allowed for a detailed understanding of the structural and functional changes within the visual pathway following PA surgery.
RESULTS
OCT findings show postoperative changes in the eye: thinning in average and nasal circumpapillary retinal nerve fiber layer, thickening in macular central 1 mm inner plexus layer, ganglion cell complex, and nasal retinal nerve fiber layer. DTI reveals increased fractional anisotropy (FA) in the left optic chiasm and posterior optic nerve, decreased mid-segment optic nerve FA, and increased apparent diffusion coefficient (ADC) in the right optic chiasm and nerve segments. Early postoperative reduction in radial peripapillary capillaries plexus density is noted. Preoperative ganglion cell layer (GCL) thickness correlates with postoperative visual radiation FA and ADC values, especially in the inferior quadrant. A negative correlation exists between preoperative GCL thickness and postoperative visual field mean defect values, particularly on the temporal side and superior inner ring. All changes are statistically significant (P < 0.05).
CONCLUSIONS
The study finds that surgery for PA has varied effects on vision. Early post surgery, there are changes in the retina and nerve signals. Macular GCL thickness before surgery might predict early visual recovery, influencing future research and treatment for vision issues related to PA.
PubMed: 38822193
DOI: 10.1007/s40123-024-00966-3 -
Scientific Reports May 2024In the animal kingdom, threat information is perceived mainly through vision. The subcortical visual pathway plays a critical role in the rapid processing of visual...
In the animal kingdom, threat information is perceived mainly through vision. The subcortical visual pathway plays a critical role in the rapid processing of visual information-induced fear, and triggers a response. Looming-evoked behavior in rodents, mimicking response to aerial predators, allowed identify the neural circuitry underlying instinctive defensive behaviors; however, the influence of disk/background contrast on the looming-induced behavioral response has not been examined, either in rats or mice. We studied the influence of the dark disk/gray background contrast in the type of rat and mouse defensive behavior in the looming arena, and we showed that rat and mouse response as a function of disk/background contrast adjusted to a sigmoid-like relationship. Both sex and age biased the contrast-dependent response, which was dampened in rats submitted to retinal unilateral or bilateral ischemia. Moreover, using genetically manipulated mice, we showed that the three type of photoresponsive retinal cells (i.e., cones, rods, and intrinsically photoresponsive retinal ganglion cells (ipRGCs)), participate in the contrast-dependent response, following this hierarchy: cones > > rods > > > ipRGCs. The cone and rod involvement was confirmed using a mouse model of unilateral non-exudative age-related macular degeneration, which only damages canonical photoreceptors and significantly decreased the contrast sensitivity in the looming arena.
Topics: Animals; Rats; Mice; Male; Retinal Ganglion Cells; Photic Stimulation; Female; Contrast Sensitivity; Behavior, Animal; Retinal Cone Photoreceptor Cells; Mice, Inbred C57BL; Visual Perception; Fear; Retina; Visual Pathways
PubMed: 38822033
DOI: 10.1038/s41598-024-63458-1 -
Neural Regeneration Research Feb 2025JOURNAL/nrgr/04.03/01300535-202502000-00034/figure1/v/2024-05-28T214302Z/r/image-tiff Several studies have found that transplantation of neural progenitor cells (NPCs)...
Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury.
JOURNAL/nrgr/04.03/01300535-202502000-00034/figure1/v/2024-05-28T214302Z/r/image-tiff Several studies have found that transplantation of neural progenitor cells (NPCs) promotes the survival of injured neurons. However, a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application. Small extracellular vesicles (sEVs) contain bioactive molecules for neuronal protection and regeneration. Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases. In this study, we intravitreally transplanted sEVs derived from human induced pluripotent stem cells (hiPSCs) and hiPSCs-differentiated NPCs (hiPSC-NPC) in a mouse model of optic nerve crush. Our results show that these intravitreally injected sEVs were ingested by retinal cells, especially those localized in the ganglion cell layer. Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration, and regulated the retinal microenvironment by inhibiting excessive activation of microglia. Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells, which had protective effects on RGCs after optic nerve injury. These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.
PubMed: 38819069
DOI: 10.4103/NRR.NRR-D-23-01414 -
PeerJ 2024Activation of the trigeminal vascular system in migraine releases vasoactive neurotransmitters, causing abnormal vasoconstriction, which may affect the ocular system,...
BACKGROUND
Activation of the trigeminal vascular system in migraine releases vasoactive neurotransmitters, causing abnormal vasoconstriction, which may affect the ocular system, leading to retinal damage. The purpose of our study was to determine whether there are differences in each retinal layer between migraine patients and healthy subjects.
METHODS
A case-control study recruited 38 migraine patients and 38 age- and sex-matched controls. Optical coherence tomography was used to measure the thickness of the peripapillary and macular retinal nerve fiber layer (pRNFL and mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL).
RESULTS
The mean ages of the migraine patients and controls were 36.29 ± 9.45 and 36.45 ± 9.27 years, respectively. Thirty-four patients (89.48%) in both groups were female. The mean disability score was 19.63 ± 20.44 (indicating severe disability). The superior-outer INL of migraine patients were thicker than controls. Thickness of the GCL at temporal-outer sector and mRNFL at the superior-outer sector of the headache-side eyes was reduced. However, the INL of the headache-side-eye showed negative correlation with the disability score. This is the first study having found thinning of the GCL and mRNFL of the headache-side eyes. The INL was also thickened in migraines but showed negative correlation with the disability score.
CONCLUSIONS
Increased INL thickness in migraine patients may result from inflammation. The more severe cases with a high disability score might suffered progressive retinal neuronal loss, resulting in thinner INL than less severe cases.
Topics: Humans; Female; Migraine Disorders; Male; Adult; Case-Control Studies; Tomography, Optical Coherence; Retina; Middle Aged; Retinal Ganglion Cells
PubMed: 38818459
DOI: 10.7717/peerj.17454 -
Frontiers in Neuroanatomy 2024Hox genes govern rostro-caudal identity along the developing spinal cord, which has a well-defined division of function between dorsal (sensory) and ventral (motor)...
INTRODUCTION
Hox genes govern rostro-caudal identity along the developing spinal cord, which has a well-defined division of function between dorsal (sensory) and ventral (motor) halves. Here we exploit developmental Hoxb8 expression, normally restricted to the dorsal cord below the obex, to genetically label spinal cord-to-brain ("spinofugal") axons.
METHODS
We crossed two targeted (knock-in) and two non-targeted recombinase-expressing lines (Hoxb8-IRES-Cre and Hoxb8-T2AFlpO; Hoxb8-Cre and Hoxb8-FlpO, respectively) with appropriate tdtomato-expressing reporter strains. Serial sectioning, confocal and superresolution microscopy, as well as light-sheet imaging was used to reveal robust labeling of ascending axons and their terminals in expected and unexpected regions.
RESULTS
This strategy provides unprecedented anatomical detail of ascending spinal tracts anterior to the brainstem, and reveals a previously undescribed decussating tract in the ventral hypothalamus (the spinofugal hypothalamic decussating tract, or shxt). The absence of Hoxb8-suppressing elements led to multiple instances of ectopic reporter expression in Hoxb8-Cre mice (retinal ganglion and vomeronasal axons, anterior thalamic nuclei and their projections to the anterior cingulate and retrosplenial cortices and subiculum, and a population of astrocytes at the cephalic flexure) and Hoxb8-FlpO mice (Cajal-Retzius cells of the dentate gyrus, and mesenchymal cells of the choroid plexus). While targeted transgenic lines were similar in terms of known spinofugal projections, Hoxb8-IRES-Cre reporters had an additional projection to the core of the facial motor nucleus, and more abundant Hoxb8-lineage microglia scattered throughout the brain than Hoxb8-T2A-FlpO (or any other) mice, suggesting dysregulated Hoxb8-driven reporter expression in one or both lines.
DISCUSSION
This work complements structural and connectivity atlases of the mouse central nervous system, and provides a platform upon which their reactions to injury or disease can be studied. Ectopic Hoxb8-driven recombinase expression may also be a useful tool to study structure and function of other cell populations in non-targeted lines.
PubMed: 38817241
DOI: 10.3389/fnana.2024.1400015 -
American Journal of Ophthalmology May 2024To compare the efficacy and safety of pars plana vitrectomy (PPV) with silicone oil compared to gas tamponade for uncomplicated rhegmatogenous retinal detachment (RRD). (Review)
Review
PURPOSE
To compare the efficacy and safety of pars plana vitrectomy (PPV) with silicone oil compared to gas tamponade for uncomplicated rhegmatogenous retinal detachment (RRD).
DESIGN
Systematic review and meta-analysis.
METHODS
A systematic literature search was conducted on Ovid MEDLINE, Embase, and the Cochrane Library from January 2000 to September 2023 for comparative studies evaluating the efficacy and safety of PPV with either silicone oil or gas tamponade in the setting of uncomplicated RRD. Our primary outcome was best-corrected visual acuity at the last study observation. Secondary outcomes included the rates of retinal reattachment, retinal thickness, and the incidence of adverse events. We performed a meta-analysis using a random-effects model.
RESULTS
Nine observational studies reporting on 491 RRD eyes were included. The mean best-corrected visual acuity at the last study observation was significantly better in the gas tamponade group than in the silicone oil group (weighted mean difference [WMD] = 0.17 logMAR, 95% confidence interval [CI] = [0.06, 0.27], P = .002). Rates of primary retinal reattachment were similar between the silicone oil and gas tamponade groups (P = .89). The ganglion cell layer was significantly thinner in the silicone oil group compared to the gas tamponade group (WMD =-3.70 µm, 95% CI = [-5.87, -1.53, P = .0008), as was the inner plexiform layer (WMD = -2.45, 95% CI = [-4.50, -0.40], P = .02) and outer nuclear layer (WMD = -11.74 µm, 95% CI = [-18.39, -5.10], P = .0005).
CONCLUSIONS
PPV with gas tamponade was associated with better functional outcomes compared to PPV with silicone oil, although both tamponades yielded comparable primary reattachment rates. The absence of randomized trials and the potential for selection bias underscore the importance of further investigation in diverse patient populations.
PubMed: 38815844
DOI: 10.1016/j.ajo.2024.05.008 -
Turkish Journal of Medical Sciences 2023This study aimed to examine changes in the thickness of individual macular retinal layers in eyes with pathological myopia (PM) and to compare the thickness of each...
BACKGROUND/AIM
This study aimed to examine changes in the thickness of individual macular retinal layers in eyes with pathological myopia (PM) and to compare the thickness of each retinal layer between the PM and control groups to gain insights into retinal perfusion.
MATERIALS AND METHODS
The study included 51 eyes in the PM group and 51 eyes in the control group. Optical coherence tomography (OCT) was used to measure the thickness of each retinal layer in the central fovea, parafoveal, and perifoveal regions. Optical coherence tomography angiography (OCT-A) was used to evaluate the retinal capillary density.
RESULTS
In the PM group, the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL) were thicker than in the control group (p = 0.004, p = 0.027, p = 0.020, and p < 0.001, respectively), whereas the outer nuclear layer (ONL) and photoreceptor layer (PRL) were thinner (p = 0.001 and p = 0.003, respectively). In other regions, the RNFL was thicker in the myopic group, whereas the GCL, IPL, INL, and ONL were thinner. OCT-A did not reveal any significant difference between the groups in terms of radial capillary plexus density (p = 0.381); however, the densities of the other plexuses were lower in the PM group.
CONCLUSIONS
The results showed alterations in the thickness of retinal layers and capillary plexus density in PM. Thus, assessment of the thickness of individual retinal layers may serve as an indicator of vascular diseases that affect the circulation of the retina and choroid.
Topics: Humans; Tomography, Optical Coherence; Male; Female; Adult; Myopia, Degenerative; Middle Aged; Macula Lutea; Retina; Retinal Vessels
PubMed: 38813500
DOI: 10.55730/1300-0144.5751 -
Frontiers in Molecular Neuroscience 2024The complex nature of the retina demands well-organized signaling to uphold signal accuracy and avoid interference, a critical aspect in handling a variety of visual... (Review)
Review
The complex nature of the retina demands well-organized signaling to uphold signal accuracy and avoid interference, a critical aspect in handling a variety of visual stimuli. A-kinase anchoring proteins (AKAPs), known for binding protein kinase A (PKA), contribute to the specificity and efficiency of retinal signaling. They play multifaceted roles in various retinal cell types, influencing photoreceptor sensitivity, neurotransmitter release in bipolar cells, and the integration of visual information in ganglion cells. AKAPs like AKAP79/150 and AKAP95 exhibit distinct subcellular localizations, impacting synaptic transmission and receptor sensitivity in photoreceptors and bipolar cells. Furthermore, AKAPs are involved in neuroprotective mechanisms and axonal degeneration, particularly in retinal ganglion cells. In particular, AKAP6 coordinates stress-specific signaling and promotes neuroprotection following optic nerve injury. As our review underscores the therapeutic potential of targeting AKAP signaling complexes for retinal neuroprotection and enhancement, it acknowledges challenges in developing selective drugs that target complex protein-protein interactions. Overall, this exploration of AKAPs provides valuable insights into the intricacies of retinal signaling, offering a foundation for understanding and potentially addressing retinal disorders.
PubMed: 38813437
DOI: 10.3389/fnmol.2024.1412407