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Indian Journal of Ophthalmology Dec 2019Melanocytoma is a deeply pigmented variant of melanocytic nevus that classically occurs in the optic disk, sometimes with contiguous involvement of the adjacent retina... (Review)
Review
Melanocytoma is a deeply pigmented variant of melanocytic nevus that classically occurs in the optic disk, sometimes with contiguous involvement of the adjacent retina or choroid. Historically, this tumor was often confused with malignant melanoma both clinically and histopathologically. Today, however, it is generally recognized by its typical clinical features that differ from most melanomas and erroneous enucleation is rarely done. Histopathologically, melanocytoma is composed of intensely pigmented round to oval nevus cells with benign features. Although traditionally believed to be a relatively stationary lesion, it is now known to exhibit minor enlargement in 10--15% of cases and can cause minor visual loss by a variety of mechanisms. In rare instance, it can induce severe visual loss due to spontaneous necrosis of the lesion or compressive optic neuropathy. More importantly, it can exhibit malignant transformation into melanoma in 1--2% of cases. Ophthalmologists should be familiar with melanocytoma of the optic disk and affected patients should be followed periodically.
Topics: Cell Transformation, Neoplastic; Humans; Melanoma; Nevus, Pigmented; Optic Disk; Optic Nerve Neoplasms
PubMed: 31755427
DOI: 10.4103/ijo.IJO_2039_19 -
Romanian Journal of Morphology and... 2022The article is a review of the latest meta-analyses regarding the genetic spectrum in schizophrenia, discussing the risks given by the disrupted-in-schizophrenia 1... (Review)
Review
The article is a review of the latest meta-analyses regarding the genetic spectrum in schizophrenia, discussing the risks given by the disrupted-in-schizophrenia 1 (DISC1), catechol-O-methyltransferase (COMT), monoamine oxidases-A∕B (MAO-A∕B), glutamic acid decarboxylase 67 (GAD67) and neuregulin 1 (NRG1) genes, and dysbindin-1 protein. The DISC1 polymorphism significantly increases the risk of schizophrenia, as well injuries from the prefrontal cortex that affect connectivity. NRG1 is one of the most important proteins involved. Its polymorphism is associated with the reduction of areas in the corpus callosum, right uncinate, inferior lateral fronto-occipital fascicle, right external capsule, fornix, right optic tract, gyrus. NRG1 and the ErbB4 receptor (tyrosine kinase receptor) are closely related to the N-methyl-D-aspartate receptor (NMDAR) (glutamate receptor). COMT is located on chromosome 22 and together with interleukin-10 (IL-10) have an anti-inflammatory and immunosuppressive function that influences the dopaminergic system. MAO gene methylation has been associated with mental disorders. MAO-A is a risk gene in the onset of schizophrenia, more precisely a certain type of single-nucleotide polymorphism (SNP), at the gene level, is associated with schizophrenia. In schizophrenia, we find deficits of the γ-aminobutyric acid (GABA)ergic neurotransmitter, the dysfunctions being found predominantly at the level of the substantia nigra. In schizophrenia, missing an allele at GAD67, caused by a SNP, has been correlated with decreases in parvalbumin (PV), somatostatin receptor (SSR), and GAD ribonucleic acid (RNA). Resulting in the inability to mature PV and SSR neurons, which has been associated with hyperactivity.
Topics: Humans; Schizophrenia; Catechol O-Methyltransferase; Receptors, N-Methyl-D-Aspartate; Polymorphism, Single Nucleotide; Monoamine Oxidase
PubMed: 36374137
DOI: 10.47162/RJME.63.2.03 -
ENeuro 2022Retinal ganglion cell (RGC) axons comprise the optic nerve and carry information to the dorsolateral geniculate nucleus (dLGN), which is then relayed to the cortex for...
Retinal ganglion cell (RGC) axons comprise the optic nerve and carry information to the dorsolateral geniculate nucleus (dLGN), which is then relayed to the cortex for conscious vision. Glaucoma is a blinding neurodegenerative disease that commonly results from intraocular pressure (IOP)-associated injury leading to RGC axonal pathology, disruption of RGC outputs to the brain, and eventual apoptotic loss of RGC somata. The consequences of elevated IOP and glaucomatous pathology on RGC signaling to the dLGN are largely unknown yet are likely to contribute to vision loss. Here, we used anatomic and physiological approaches to study the structure and function of retinogeniculate (RG) synapses in male and female DBA/2J (D2) mice with inherited glaucoma before and after IOP elevation. D2 mice showed progressive loss of anterograde optic tract transport to the dLGN and vGlut2 labeling of RGC axon terminals while patch-clamp measurements of RG synaptic function showed that synaptic transmission was reduced in 9-month and 12-month D2 mice because of the loss of individual RGC axon inputs. TC neuron dendrites had reduced Sholl complexity at 12 months, suggestive of delayed reorganization following reduced synaptic input. There was no detectable change in RGC density in 11- to 12-month D2 retinas, quantified as the number of ganglion cell layer-residing somata immuno-positive for NeuN and immuno-negative for the amacrine marker choline acetyltransferase (ChAT). Thus, observed synaptic defects appear to precede RGC somatic loss. These findings identify glaucoma-associated and IOP-associated deficits in an important subcortical RGC projection target, shedding light on processes linking IOP to vision loss.
Topics: Mice; Animals; Male; Female; Mice, Inbred DBA; Neurodegenerative Diseases; Glaucoma; Retina; Retinal Ganglion Cells; Disease Models, Animal
PubMed: 36526366
DOI: 10.1523/ENEURO.0421-22.2022 -
The Journal of Neuroscience : the... Aug 2022Individual differences among human brains exist at many scales, spanning gene expression, white matter tissue properties, and the size and shape of cortical areas. One...
Individual differences among human brains exist at many scales, spanning gene expression, white matter tissue properties, and the size and shape of cortical areas. One notable example is an approximately 3-fold range in the size of human primary visual cortex (V1), a much larger range than is found in overall brain size. A previous study (Andrews et al., 1997) reported a correlation between optic tract (OT) cross-section area and V1 size in postmortem human brains, suggesting that there may be a common developmental mechanism for multiple components of the visual pathways. We evaluated the relationship between properties of the OT and V1 in a much larger sample of living human brains by analyzing the Human Connectome Project (HCP) 7 Tesla Retinotopy Dataset (including 107 females and 71 males). This dataset includes retinotopic maps measured with functional MRI (fMRI) and fiber tract data measured with diffusion MRI (dMRI). We found a negative correlation between OT fractional anisotropy (FA) and V1 surface area ( = -0.19). This correlation, although small, was consistent across multiple dMRI datasets differing in acquisition parameters. Further, we found that both V1 surface area and OT properties were correlated among twins, with higher correlations for monozygotic (MZ) than dizygotic (DZ) twins, indicating a high degree of heritability for both properties. Together, these results demonstrate covariation across individuals in properties of the retina (OT) and cortex (V1) and show that each is influenced by genetic factors. The size of human primary visual cortex (V1) has large interindividual differences. These differences do not scale with overall brain size. A previous postmortem study reported a correlation between the size of the human optic tract (OT) and V1. In this study, we evaluated the relationship between the OT and V1 in living humans by analyzing a neuroimaging dataset that included functional MRI (fMRI) and diffusion MRI (dMRI) data. We found a small, but robust correlation between OT tissue properties and V1 size, supporting the existence of structural covariance between the OT and V1 in living humans. The results suggest that characteristics of retinal ganglion cells (RGCs), reflected in OT measurements, are correlated with individual differences in human V1.
PubMed: 35853720
DOI: 10.1523/JNEUROSCI.0043-22.2022 -
The Journal of Comparative Neurology Oct 2021In 1994, Burrill and Easter described the retinal projections in embryonic and larval zebrafish, introducing the term "arborization fields" (AFs) for the retinorecipient... (Review)
Review
In 1994, Burrill and Easter described the retinal projections in embryonic and larval zebrafish, introducing the term "arborization fields" (AFs) for the retinorecipient areas. AFs were numbered from 1 to 10 according to their positions along the optic tract. With the exception of AF10 (neuropil of the optic tectum), annotations of AFs remained tentative. Here we offer an update on the likely identities and functions of zebrafish AFs after successfully matching classical neuroanatomy to the digital Max Planck Zebrafish Brain Atlas. In our system, individual AFs are neuropil areas associated with the following nuclei: AF1 with the suprachiasmatic nucleus; AF2 with the posterior parvocellular preoptic nucleus; AF3 and AF4 with the ventrolateral thalamic nucleus; AF4 with the anterior and intermediate thalamic nuclei; AF5 with the dorsal accessory optic nucleus; AF7 with the parvocellular superficial pretectal nucleus; AF8 with the central pretectal nucleus; and AF9d and AF9v with the dorsal and ventral periventricular pretectal nuclei. AF6 is probably part of the accessory optic system. Imaging, ablation, and activation experiments showed contributions of AF5 and potentially AF6 to optokinetic and optomotor reflexes, AF4 to phototaxis, and AF7 to prey detection. AF6, AF8 and AF9v respond to dimming, and AF4 and AF9d to brightening. While few annotations remain tentative, it is apparent that the larval zebrafish visual system is anatomically and functionally continuous with its adult successor and fits the general cyprinid pattern. This study illustrates the synergy created by merging classical neuroanatomy with a cellular-resolution digital brain atlas resource and functional imaging in larval zebrafish.
Topics: Animals; Brain Mapping; Pretectal Region; Retina; Superior Colliculi; Visual Pathways; Zebrafish
PubMed: 34180059
DOI: 10.1002/cne.25204 -
American Journal of Ophthalmology Case... Jun 2022To report a case of bilateral Vogt-Koyanagi-Harada (VKH)-like granulomatous pan uveitis secondary to brentuximab vedotin (BV) administration to treat for classical...
PURPOSE
To report a case of bilateral Vogt-Koyanagi-Harada (VKH)-like granulomatous pan uveitis secondary to brentuximab vedotin (BV) administration to treat for classical Hodgkin lymphoma (CHL).
OBSERVATIONS
A case of bilateral pan uveitis is described, following administration of BV, with features of VKH-like uveitis: presence of inflammatory cells in the anterior and posterior segment, multiple small serous detachments around the optic disc and retinal pigment epithelium (RPE) folds confirmed by optical coherence tomography (OCT) as well as hypocyanesent dark dots, disc hyperfluorescence and fuzzy vascular patterns seen on indocyanine green and fluorescein angiography. There were no systemic features of VKH disease. Further etiological investigation showed no clear infectious or inflammatory cause. The uveitis responded well to treatment with corticosteroids and cessation of BV. A relapse occurred a few months later when BV treatment was reinitiated, suggesting a probable adverse event to this drug, according to the Naranjo algorithm.
CONCLUSIONS
We hypothesize that administration of BV can induce a VKH-like uveitis, caused by loss of function of protective CD30 cells present in the uveal tract, possibly aggravated by collateral damage to surrounding CD30cells and melanocytes, leading to a uveal immune reaction. It is therefore important for the clinicians using BV to be aware of this adverse event. Growing experience with immunotherapy will provide more clinical insights in these complex immune mechanisms in the future.
PubMed: 35243175
DOI: 10.1016/j.ajoc.2022.101440 -
Cell Reports Aug 2023The balance of contralateral and ipsilateral retinogeniculate projections is critical for binocular vision, but the transcriptional programs regulating this process...
The balance of contralateral and ipsilateral retinogeniculate projections is critical for binocular vision, but the transcriptional programs regulating this process remain ill defined. Here we show that the Pou class homeobox protein POU3F1 is expressed in nascent mouse contralateral retinal ganglion cells (cRGCs) but not ipsilateral RGCs (iRGCs). Upon Pou3f1 inactivation, the proportion of cRGCs is reduced in favor of iRGCs, leading to abnormal projection ratios at the optic chiasm. Conversely, misexpression of Pou3f1 in progenitors increases the production of cRGCs. Using CUT&RUN and RNA sequencing in gain- and loss-of-function assays, we demonstrate that POU3F1 regulates expression of several key members of the cRGC gene regulatory network. Finally, we report that POU3F1 is sufficient to induce RGC-like cell production, even in late-stage retinal progenitors of Atoh7 knockout mice. This work uncovers POU3F1 as a regulator of the cRGC transcriptional program, opening possibilities for optic nerve regenerative therapies.
PubMed: 37590135
DOI: 10.1016/j.celrep.2023.112985 -
Endocrine Reviews May 2024Since hypothalamic obesity (HyOb) was first described over 120 years ago by Joseph Babinski and Alfred Fröhlich, advances in molecular genetic laboratory techniques... (Review)
Review
Since hypothalamic obesity (HyOb) was first described over 120 years ago by Joseph Babinski and Alfred Fröhlich, advances in molecular genetic laboratory techniques have allowed us to elucidate various components of the intricate neurocircuitry governing appetite and weight regulation connecting the hypothalamus, pituitary gland, brainstem, adipose tissue, pancreas, and gastrointestinal tract. On a background of an increasing prevalence of population-level common obesity, the number of survivors of congenital (eg, septo-optic dysplasia, Prader-Willi syndrome) and acquired (eg, central nervous system tumors) hypothalamic disorders is increasing, thanks to earlier diagnosis and management as well as better oncological therapies. Although to date the discovery of several appetite-regulating peptides has led to the development of a range of targeted molecular therapies for monogenic obesity syndromes, outside of these disorders these discoveries have not translated into the development of efficacious treatments for other forms of HyOb. This review aims to summarize our current understanding of the neuroendocrine physiology of appetite and weight regulation, and explore our current understanding of the pathophysiology of HyOb.
Topics: Humans; Obesity; Hypothalamic Diseases; Appetite; Neurosecretory Systems; Animals; Hypothalamus; Body Weight
PubMed: 38019584
DOI: 10.1210/endrev/bnad033 -
Ocular Oncology and Pathology Dec 2021Hodgkin lymphoma (HL) is a hematopoietic neoplasm characterized by cancerous Reed-Sternberg cells. In contrast to ophthalmic manifestations by non-HL that are well... (Review)
Review
BACKGROUND
Hodgkin lymphoma (HL) is a hematopoietic neoplasm characterized by cancerous Reed-Sternberg cells. In contrast to ophthalmic manifestations by non-HL that are well recognized, there is paucity of the literature as it relates to ophthalmic manifestation by HL. We performed a comprehensive review of published studies (case reports and small case series) to characterize the ophthalmic manifestations of HL.
SUMMARY
Thirty patients were identified with ophthalmic manifestation of HL. Thirteen (43%) were male, and 14 (46%) were female (in 3 cases, sex was not specified). The median age at ophthalmic presentation was 27 years. Diagnosis of HL was made after ophthalmic manifestation in 10 (33%) cases, whereas 11 (36%) cases had a prior diagnosis of HL. Ophthalmic manifestations can be classified into 3 main groups; direct infiltration, inflammatory reaction, and paraneoplastic process. Seven cases had infiltration of the optic nerve. Uveal inflammatory reaction was reported in 21 cases. The presence of intraocular Reed-Sternberg cells had been confirmed in 1 case with granulomatous uveitis. Conjunctival and corneal reaction was seen in 3 cases. HL was in stage 2 or higher, with only 1 case with stage 1A (12 cases HL stage not specified). Seven cases (22%) died of HD, all were diagnosed with advanced lymphoma, and none was treated with chemotherapy.
KEY MESSAGE
Ocular involvement in HL is extremely rare. A few cases of histopathologically confirmed optic nerve/tract infiltration are within the spectrum of CNS involvement by HL. Inflammatory uveitis is the most common ophthalmic association of HL. In the presence of prior known diagnosis of HL, restaging should be considered to exclude recurrence. Toxicity or adverse reaction to drugs used to treat HL may also contribute to ophthalmic involvement.
PubMed: 35087814
DOI: 10.1159/000519032 -
International Journal of Environmental... Nov 2021Wolfram Syndrome (WS) is a rare neurodegenerative disease with autosomal recessive inheritance and characterized by juvenile onset, non-autoimmune diabetes mellitus and... (Review)
Review
Wolfram Syndrome (WS) is a rare neurodegenerative disease with autosomal recessive inheritance and characterized by juvenile onset, non-autoimmune diabetes mellitus and later followed by optic atrophy leading to blindness, diabetes insipidus, hearing loss, and other neurological and endocrine dysfunctions. A wide spectrum of neurodegenerative abnormalities affecting the central nervous system has been described. Among these complications, neurogenic bladder and urodynamic abnormalities also deserve attention. Urinary tract dysfunctions (UTD) up to end stage renal disease are a life-threatening complication of WS patients. Notably, end stage renal disease is reported as one of the most common causes of death among WS patients. UTD have been also reported in affected adolescents. Involvement of the urinary tract occurs in about 90% of affected patients, at a median age of 20 years and with peaks at 13, 21 and 33 years. The aim of our narrative review was to provide an overview of the most important papers regarding urological impairment in Wolfram Syndrome. A comprehensive search on PubMed including Wolfram Syndrome and one or more of the following terms: chronic renal failure, bladder dysfunction, urological aspects, and urinary tract dysfunction, was done. The exclusion criteria were studies not written in English and not including urinary tract dysfunction deep evaluation and description. Studies mentioning general urologic abnormalities without deep description and/or follow-up were not considered. Due to the rarity of the condition, we considered not only papers including pediatric patients, but also papers with pediatric and adult case reports.
Topics: Adolescent; Adult; Child; Humans; Neurodegenerative Diseases; Optic Atrophy; Urinary Tract; Urodynamics; Wolfram Syndrome; Young Adult
PubMed: 34831749
DOI: 10.3390/ijerph182211994