Intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin belong to a heterogenic population of RGCs which regulate the circadian clock, masking behavior, ...melatonin suppression, the pupillary light reflex, and sleep/wake cycles. The different functions seem to be associated to different subtypes of melanopsin cells. In rodents, subtype classification has associated subtypes to function. In primate and human retina such classification has so far, not been applied. In the present study using antibodies against N‐ and C‐terminal parts of human melanopsin, confocal microscopy and 3D reconstruction of melanopsin immunoreactive (‐ir) RGCs, we applied the criteria used in mouse on human melanopsin‐ir RGCs. We identified M1, displaced M1, M2, and M4 cells. We found two other subtypes of melanopsin‐ir RGCs, which were named “gigantic M1 (GM1)” and “gigantic displaced M1 (GDM1).” Few M3 cells and no M5 subtypes were labeled. Total cell counts from one male and one female retina revealed that the human retina contains 7283 ± 237 melanopsin‐ir (0.63–0.75% of the total number of RGCs). The melanopsin subtypes were unevenly distributed. Most significant was the highest density of M4 cells in the nasal retina. We identified input to the melanopsin‐ir RGCs from AII amacrine cells and directly from rod bipolar cells via ribbon synapses in the innermost ON layer of the inner plexiform layer (IPL) and from dopaminergic amacrine cells and GABAergic processes in the outermost OFF layer of the IPL. The study characterizes a heterogenic population of human melanopsin‐ir RGCs, which most likely are involved in different functions.
Melanopsin immunoreactive retinal ganglion cells (mRGCs) in the human retina were sub‐classified as in mice reveling the M1, ‐ displaced M1, ‐ M2 and ‐M4 cells subtype. Furthermore, the human retina contain gigantic M1 ‐ and gigantic displaced M1 cells not previously found in mice. Total cell counts, distribution and innervation from AII, ‐ GABAergic and dopaminergic amacrine cells and direct innervation from rod bipolar cells demonstrate the hetrogenesis of the human melanopsin mRGCs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Human papillomaviruses (HPV) are a large group of DNA viruses that infect the basal cells of the stratified epithelium at different anatomic locations. In the ocular adnexal region, the mucosa of the ...conjunctiva and the lacrimal drainage system, as well as the eyelid skin, are potential locations for HPV-related neoplasia. The role of HPV in squamous cell neoplasia of the ocular adnexa has been debated for several decades. Due to the rarity of all these tumors, large studies are not available in the scientific literature, thereby hampering the precision of the HPV prevalence estimates and the ability to conclude. Nevertheless, increasing evidence supports that defined subsets of conjunctival papillomas, intraepithelial neoplasia, and carcinomas develop in an HPV-dependent pathway. The role of HPV in squamous cell tumors arising in the lacrimal drainage system and the eyelid is still uncertain. Further, the potential of HPV status as a diagnostic, prognostic, or predictive biomarker in these diseases is a topic for future research.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Although identified as the key environmental driver of common cutaneous melanoma, the role of ultraviolet radiation (UVR)-induced DNA damage in mucosal melanoma is poorly defined. We analyze 10 ...mucosal melanomas of conjunctival origin by whole genome sequencing and our data shows a predominance of UVR-associated single base substitution signature 7 (SBS7) in the majority of the samples. Our data shows mucosal melanomas with SBS7 dominance have similar genomic patterns to cutaneous melanomas and therefore this subset should not be excluded from treatments currently used for common cutaneous melanoma.
Multiple studies have shown overwhelming evidence supporting the impairment of melanopsin function due to glaucoma. However, few studies have been carried out in humans analyzing the histology of ...melanopsin-expressing retinal ganglion cells (mRGCs) in retinas with glaucoma. The aim of this study was to analyze the pattern of expression of mRGCs relative to RGCs in the normal retina and retinas harboring varying stages of glaucoma.
Paraffin-embedded human donor eyes with glaucoma (n = 11) and age-matched controls (n = 10) were obtained from Department of Pathology at Rigshospital (Copenhagen, Denmark) for detection of RNA binding protein with multiple splicing (RBPMS) and melanopsin by immunohistochemistry. The density of RBPMS-expressing RGCs and mRGCs in each retina was estimated as the total cell count in the total retinal area analyzed (cell counts/mm2).
No significant difference was observed in mRGC expression in the normal retinas and mild-staged retinas with glaucoma; the densities of mRGCs were 3.08 ± 0.47 and 3.00 ± 0.13 cell counts/mm2, respectively. However, the severely staged retinas with glaucoma showed a significant loss in mRGCs density, 1.09 ± 0.35 cell counts/mm2, with 75% of all retained mRGCs occurring in the inner nuclear layer.
This is the first report illustrating histologic evidence for reduced mRGC density in the ganglion cell layer of retinas with severely staged glaucoma compared with age-matched controls. This result proposes evaluation of mRGCs integrity as a basis for assessing the pathophysiologic disease progression of glaucoma.
The orbit can harbor mass lesions of various cellular origins. The symptoms vary considerably according to the nature, location, and extent of the disease and include common signs of proptosis, globe ...displacement, eyelid swelling, and restricted eye motility. Although radiological imaging tools are improving, with each imaging pattern having its own differential diagnosis, orbital mass lesions often pose a diagnostic challenge. To provide an accurate, specific, and sufficiently comprehensive diagnosis, to optimize clinical management and estimate prognosis, pathological examination of a tissue biopsy is essential. Diagnostic orbital tissue biopsy is obtained through a minimally invasive orbitotomy procedure or, in selected cases, fine needle aspiration. The outcome of successful biopsy, however, is centered on its representativeness, processing, and interpretation. Owing to the often small volume of the orbital biopsies, artifacts in the specimens should be limited by careful peroperative tissue handling, fixation, processing, and storage. Some orbital lesions can be characterized on the basis of cytomorphology alone, whereas others need ancillary molecular testing to render the most reliable diagnosis of therapeutic, prognostic, and predictive value. Herein, we review the diagnostic algorithm for orbital mass lesions, using clinical, radiological, and pathological recommendations, and discuss the methods and potential pitfalls in orbital tissue biopsy acquisition and analysis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
IntroductionSebaceous gland carcinoma (SGC) of the eyelid is an aggressive tumour with the ability to metastasise and an increased morbidity. Controversies regarding the epidemiology of this ...malignant eyelid tumour is widespread in the scientific literature. Western reports repeatedly describes eyelid SGC as a rare occurring tumour in general, accounting for 1%–3% of all eyelid tumours, however studies from Asia have uncovered a higher frequency of eyelid SGC including 54% of all eyelid tumours in Japan, and 43%–56% in India. We wish to retrieve observational data of eyelid SGC prevalence in proportion to total eyelid tumours, from pathological studies published worldwide to resolve this controversy.Methods and analysisWe will search Ovid Medline, EMBASE, Cochrane Central Register of Controlled Trials, Scopus and Google Scholar to identify published reports on eyelid SGC prevalence proportions, aiming to clarify the incidence of the tumour. We will include observational clinicopathological studies reporting prevalence with confirmed histopathology. No limitations on publication date or language will be applied. Data from the individual studies and study quality will be extracted by two individual reviewers. Study quality will be assessed using the JBI Critical Appraisal Instrument for Studies Reporting Prevalence Data. Raw proportions will be transformed and pooled using a random effects model for meta-analysis. And subgroup analysis according to geography will be performed. If data are deemed unsuitable for a meta-analysis, a narrative synthesis will be presented. We will judge the certainty of evidence and present whether this has an overall effect on the results. The results may shed light on a long-standing academic disparity of the scientific literature.Ethics and disseminationThis systematic review does not require ethical approval. The results of this proposed review will be the subject to a publication in an international peer-reviewed journal within the ophthalmic or pathological specialty.PROSPERO registration numberCRD42023487141.
Lymphoma of the Eyelid Svendsen, Frederik Holm, MB; Heegaard, Steffen, MD, DMSc
Survey of ophthalmology,
05/2017, Volume:
62, Issue:
3
Journal Article
Peer reviewed
Abstract Lymphoma of the eyelid constitutes 5% of ocular adnexal lymphoma. In previously published cases, 56% of lymphomas of the eyelid are of B-cell origin and 44% are of T-cell origin. The most ...frequent B-cell lymphomas are extranodal marginal zone lymphoma (27 cases--14%) and diffuse large B-cell lymphoma (18 cases--9%). T-cell lymphomas are most frequently mycosis fungoides (25 cases--13%), extranodal NK/T-cell, nasal type lymphoma (12 cases--6%) and primary cutaneous anaplastic large cell lymphoma (12 cases--6%). This distribution differs from the distribution of ocular adnexal lymphoma and that of cutaneous lymphoma. The majority of subtypes occur in elderly patients, except for lymphoblastic lymphoma of B-cell and T-cell origin and Burkitt lymphoma, which occur in children and adolescents. Several subtypes have a male predominance, including peripheral T-cell lymphoma and Burkitt lymphoma. Only lymphomatoid papulosis has a female predominance. Signs of B-cell and T-cell lymphomas are tumor and/or swelling of the eyelid. Ulceration and erythema occur frequently among patients with T-cell lymphoma. Radiotherapy with or without surgery is the treatment of choice for low-grade, solitary lymphomas, whereas chemotherapy with or without adjuvant treatment is the treatment of choice for high-grade and/or disseminated lymphomas. The majority of subtypes, especially low-grade subtypes, have a good prognosis with few recurrences or progression. Some subtypes, including mycosis fungoides, have a poorer prognosis. Extranodal NK/T-cell lymphoma, nasal type has an exceedingly poor prognosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Lens crystallines are special proteins in the eye lens. Because the epithelial basement membrane (lens capsule) completely encloses the lens, desquamation of aging cells is impossible, and due to the ...complete absence of blood vessels or transport of metabolites in this area, there is no subsequent remodelling of these fibers, nor removal of degraded lens fibers. Human tissue ultimately derives its (14)C content from the atmospheric carbon dioxide. The (14)C content of the lens proteins thus reflects the atmospheric content of (14)C when the lens crystallines were formed. Precise radiocarbon dating is made possible by comparing the (14)C content of the lens crystallines to the so-called bomb pulse, i.e. a plot of the atmospheric (14)C content since the Second World War, when there was a significant increase due to nuclear-bomb testing. Since the change in concentration is significant even on a yearly basis this allows very accurate dating.
Our results allow us to conclude that the crystalline formation in the lens nucleus almost entirely takes place around the time of birth, with a very small, and decreasing, continuous formation throughout life. The close relationship may be further expressed as a mathematical model, which takes into account the timing of the crystalline formation.
Such a life-long permanence of human tissue has hitherto only been described for dental enamel. In confront to dental enamel it must be held in mind that the eye lens is a soft structure, subjected to almost continuous deformation, due to lens accommodation, yet its most important constituent, the lens crystalline, is never subject to turnover or remodelling once formed. The determination of the (14)C content of various tissues may be used to assess turnover rates and degree of substitution (for example for brain cell DNA). Potential targets may be nervous tissues in terms of senile or pre-senile degradation, as well as other highly specialised structures of the eyes. The precision with which the year of birth may be calculated points to forensic uses of this technique.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Melanoma of the ocular region (ocular melanoma) comprises about 5% of all patients with melanoma and covers posterior uveal melanoma, iris melanoma, and conjunctival melanoma. The risk of metastasis ...is much higher in patients with ocular melanoma compared to a primary melanoma of the skin. The subtypes of ocular melanoma have distinct genetic features, which should be taken into consideration when making clinical decisions. Most relevant for current practice is the absence of
mutations in posterior uveal melanoma, although present in some iris melanomas and conjunctival melanomas. In this review, we discuss the genetic biomarkers of the subtypes of ocular melanoma and their impacts on the clinical care of these patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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