117 research outputs found
Morphological characterization and clinical effects of stromal alterations after intracorneal ring segment implantation in keratoconus
Purpose To analyze the histological and (ultra)structural stromal tissue changes after femtosecond (Fs) laser–assisted intra corneal ring segment (ICRS) implantation and their refractive and topographic efects in patients with keratoconus.
Methods This monocentric retrospective case series included 15 consecutive patients with clinical peri-segmental lamellar
channel deposits after treatment with Fs-ICRS implantation for keratoconus. The stromal changes were investigated using
in vivo confocal microscopy. Two patients underwent a penetrating keratoplasty after the Fs-ICRS implantation; the explanted
corneas were processed for histopathology and transmission electron microscopy (TEM). Refractive and topographic efects
were investigated comparing the uncorrected (UDVA) and corrected (CDVA) distance visual acuity, spherical equivalent
(SE), fat (K1), steep (K2), and steepest (Kmax) keratometry before and after detection of lamellar channel deposits.
Results In vivo confocal microscopy revealed difuse linear and focal granular hyperrefective structures. Histologically,
there was mild proliferation of fbroblasts and fbrosis. TEM demonstrated focal accumulations of degenerated keratocytes
with cytoplasmic lipid inclusions. There were no signifcant changes for UDVA (Δ=0.0±0.2 logMAR; p=0.67), CDVA
(Δ=0.0±0.1 logMAR; p=0.32), SE (Δ 0.1±0.9 D; p=0.22), K1 (Δ=0.3±1.0 D; p=0.28), K2 (Δ=0.1±0.9 D; p=0.51),
and Kmax (Δ=0.3±1.5 D; p=0.17).
Conclusions Two types of structural stromal changes were identifed: (1) difuse peri-segmental fbrosis and (2) lamellar
channel deposits. These structural changes showed no evidence of a relevant refractive or topographic efect
Recurrence of paraproteinemic keratopathy after penetrating keratoplasty and its assessment with confocal microscopy
Purpose
To report on a case of recurrence of paraproteinemic keratopathy (PPK) associated with monoclonal gammopathy after bilateral penetrating keratoplasty.
Observations
Penetrating keratoplasty was performed on both eyes of a 45-year-old man due to bilateral progressive corneal stromal clouding. Recurrence of the corneal stromal opacities accompanied by a decrease in visual acuity was observed on slit-lamp examination already two years after penetrating keratoplasty. Confocal laser scanning microscopy (CLSM) of the corneal grafts performed three years after penetrating keratoplasty showed bilateral morphological changes identical to that found in the patient's corneas prior to penetrating keratoplasty. A hematological work-up revealed monoclonal gammopathy of type IgG kappa. The histochemical examination of the explanted corneas confirmed the diagnosis of PPK.
Conclusions and importance
Paraproteinemic keratopathy is an underdiagnosed ophthalmological condition, which may be associated with potentially life-threatening hematologic disorders. A hematological workup should be performed in patients with corneal opacities of uncertain etiology. Penetrating keratoplasty should be performed with caution in patients with monoclonal gammopathy due to the possibility of a very fast recurrence of PPK in the corneal graft. This is the first presentation of the recurrence of flake like PPK after penetrating keratoplasty assessed with CLSM
Corneal epithelial ingrowth after perforating corneal injury: a case report
Background Epithelial ingrowth is a rare complication after ocular perforation and can become manifest many years
after the primary trauma.
Case presentation A 49-year-old patient presented with a positive Seidel test of unclear origin at her left eye, as
well as a sharply defned anterior-stromal corneal scar at both eyes. Prior operations included a bilateral laser-assisted
blepharoplasty 3 months earlier. The patient indicated to have been on holiday to France 5 months earlier, during an
ongoing oak processionary moth caterpillars infestation.
The examination using confocal microscopy confrmed a corneal perforation at the left eye and revealed corneal
epithelial ingrowth capped with scarred stroma in both eyes. We performed a penetrating keratoplasty at the left eye.
The scarred and perforated host cornea was divided into 4 pieces for further investigation: microbiology (negative),
virology (negative), histology and transmission electron microscopy (TEM). Histology revealed diferently structured
epithelium, centrally inverted into the stroma through defects in Bowman’s layer. TEM revealed full thickness corneal
perforation with an epithelial plug extending to the lower third of the cornea, but without evidence of epithelial cell
migration into the anterior chamber.
Our diferential diagnosis of the unclear positive Seidel test with epithelial ingrowth was as follows: (1) corneal perfo‑
ration by hairs of the oak processionary moth caterpillar, although no hairs could be found histologically; (2) corneal
perforation during laser-assisted blepharoplasty, which may be supported by the presence of pigmented cells on the
posterior surface of Descemet´s membrane, pointing to a possible iris injury.
Conclusion Consequently, we highlighted that contact lenses can be useful, safe and inexpensive protective devices
in upper eyelid procedures to protect the cornea against mechanical iatrogenic trauma
Autoantibodies Activating the β2-Adrenergic Receptor Characterize Patients With Primary and Secondary Glaucoma
Recently, agonistic autoantibodies (agAAb) activating the β2-adrenergic receptor were detected in primary open-angle glaucoma (POAG) or ocular hypertension (OHT) patients and were linked to intraocular pressure (IOP) (1). The aim of the present study was to quantify β2-agAAb in the sera of glaucoma suspects and patients with primary and secondary glaucoma. Patients with OHT (n = 33), pre-perimetric POAG (pre-POAG; n = 11), POAG (n = 28), and 11 secondary OAG (SOAG) underwent ophthalmological examinations including examinations with Octopus G1 perimetry and morphometry. Twenty-five healthy individuals served as controls. Serum-derived IgG samples were analyzed for β2-agAAb using a functional bioassay. The beat-rate-increase of spontaneously beating cultured neonatal rat cardiomyocytes was monitored with 1.6 beats/15 s as cut-off. None of the sera of normal subjects showed β2-agAAb. In POAG or OHT patients increased beating rates of 4.1 ± 2.2 beats/15 s, and 3.7 ± 2.8 beats/15 s were detected (p > 0.05). Glaucoma patients with (POAG) and without perimetric (pre-POAG) defects did not differ (pre-POAG 4.4 ± 2.6 beats/15 s, POAG 4.1 ± 2.0 beats/15 s, p > 0.05). Patients with SOAG yielded mean beating rates of 4.7 ± 1.7 beats/15 s (p > 0.05). β2-agAAb were seen in 73% of OHT, 82% of pre-POAG, 82% of POAG, and 91% SOAG patients (p 0.05). The robust β2-agAAb seropositivity in patients with OHT, pre-POAG, POAG, and SOAG suggest a primary common role for β2-agAAb starting early in glaucoma pathophysiology and turned out to be a novel marker identifying all patients with increased IOP independent of glaucoma stage and entity
Sustained activation of the unfolded protein response induces cell death in Fuchs' endothelial corneal dystrophy
Purpose: The unfolded protein response (UPR) is believed to play a role in the pathogenesis of Fuchs' endothelial corneal dystrophy (FECD). The purpose of this study was to investigate whether unfolded proteins accumulate in the corneal endothelium in FECD and if they are involved in triggering cell death. Methods: Descemet's membranes with corneal endothelial cells (CECs) were obtained during keratoplasty, and expression of aggresomes, type 1 collagen, fibronectin, and agrin was evaluated. Endoplasmic reticulum (ER) stress of immortalized human CECs from non-FECD subjects and from FECD patients (iHCEC and iFECD, respectively) were evaluated. The effect of MG132-mediated aggresome formation on the UPR and intrinsic pathway and the effect of mitochondrial damage on UPR were also examined. The effect of CHOP knockdown on the ER stress–mediated intrinsic pathway was also evaluated. Results: Aggresome formation was higher in iFECD than in iHCEC and was colocalized with type 1 collagen, fibronectin, and agrin. GRP78, phosphorylated IRE1, PERK, and CHOP showed higher activation in iFECD than in iHCEC. MG132-mediated aggresome formation upregulated ER stress sensors, the mitochondrial membrane potential drop, cytochrome c release to the cytoplasm, and activation of caspase-9 and -3. By contrast, staurosporine-mediated mitochondrial damage did not induce ER stress. Knockdown of CHOP attenuated the ER stress-induced cleavage of caspase-9, which is caused by intrinsic pathway activation. Conclusions: Excessive synthesis of extracellular matrix proteins induced unfolded protein accumulation in FECD. Prolonged ER stress–mediated cell death, occurring via the intrinsic apoptotic signaling pathway, therefore might be associated with the pathogenesis of FECD
ER-stress and basement membrane defects combine to cause glomerular and tubular renal disease caused by Col4a1 mutations
Collagen IV is a major component of basement membranes, and mutations in COL4A1, which encodes collagen IV alpha chain 1, cause a multisystemic disease encompassing cerebrovascular, eye and kidney defects. However, COL4A1 renal disease remains poorly characterized and its pathomolecular mechanisms are unknown. We show that Col4a1 mutations in mice cause hypotension and renal disease, including proteinuria and defects in Bowman's capsule and the glomerular basement membrane, indicating a role for Col4a1 in glomerular filtration. Impaired sodium reabsorption in the loop of Henle and distal nephron despite elevated aldosterone levels indicates that tubular defects contribute to the hypotension, highlighting a novel role for the basement membrane in vascular homeostasis by modulation of the tubular response to aldosterone. Col4a1 mutations also cause diabetes insipidus, whereby the tubular defects lead to polyuria associated with medullary atrophy and a subsequent reduction in the ability to upregulate aquaporin 2 and concentrate urine. Moreover, haematuria, haemorrhage and vascular basement membrane defects confirm an important vascular component. Interestingly, although structural and compositional basement membrane defects occurred in the glomerulus and Bowman's capsule, no tubular basement membrane defects were detected. By contrast, medullary atrophy was associated with chronic ER stress, providing evidence for cell-type-dependent molecular mechanisms of Col4a1 mutations. These data show that both basement membrane defects and ER stress contribute to Col4a1 renal disease, which has important implications for the development of treatment strategies for collagenopathies
Совершенствование системы делопроизводства угольной компании
В процессе исследования проводилось изучение содержания понятий "делопроизводство" и "документационное обеспечение управления"; исследование нормативно – правовой базы современного делопроизводства, принципов его организации; изучение цели, задач, функций и назначения службы делопроизводства; анализировалась система делопроизводства ООО "Угольная компания "Заречная"; были выработаны рекомендации по совершенствованию системы документационного обеспечения управления. Результаты исследования и выработанные рекомендации были внедрены в практику работы ООО "Угольная компания "Заречная".In the course of the research, the content of the notions of "office work" and "document management provision" was studied; research of the legal base of modern office work, principles of its organization; the study of the purpose, tasks, functions and appointment of the office work; the system of record keeping of LLC "Coal Company "Zarechnaya" was analyzed; Recommendations were developed to improve the system of document management support. The results of the study and the recommendations developed were introduced into the practice of the LLC "Coal Company "Zarechnaya "
Retinal regions shape human and murine Müller cell proteome profile and functionality
The human macula is a highly specialized retinal region with pit‐like morphology and rich in cones. How Müller cells, the principal glial cell type in the retina, are adapted to this environment is still poorly understood. We compared proteomic data from cone‐ and rod‐rich retinae from human and mice and identified different expression profiles of cone‐ and rod‐associated Müller cells that converged on pathways representing extracellular matrix and cell adhesion. In particular, epiplakin (EPPK1), which is thought to play a role in intermediate filament organization, was highly expressed in macular Müller cells. Furthermore, EPPK1 knockout in a human Müller cell‐derived cell line led to a decrease in traction forces as well as to changes in cell size, shape, and filopodia characteristics. We here identified EPPK1 as a central molecular player in the region‐specific architecture of the human retina, which likely enables specific functions under the immense mechanical loads in vivo
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