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Epithelial–mesenchymal transition‐related serum markers ET‐1, IL‐8 and TGF‐β2 are elevated in a Finnish wet age‐related macular degeneration cohort

Liukkonen, Mikko P. K. ; Paterno, Jussi J. ; Kivinen, Niko ; [et al.]

Wiley ; 2022

In: Acta Ophthalmologica Vol. 100, No. 5 ( 2022-08)

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In: Acta Ophthalmologica, Wiley, Vol. 100, No. 5 ( 2022-08)

Abstract: It has been hypothesized that epithelial–mesenchymal transition (EMT) may occur in the retinal pigment epithelium of advanced stage age‐related macular degeneration (AMD). Various serum and plasma growth factors and inflammatory mediators have been linked to AMD. We were interested in finding out whether systemic levels of EMT‐associated markers were altered in the serum of wet AMD patients. Serum biomarkers associated with the various pathological processes of AMD may present an avenue towards identifying and characterizing the birth mechanisms of wet AMD, its progression and severity, paving the way towards the application of precision medicine. Methods We chose to measure the serum levels of known biomarkers of EMT – EGF (epidermal growth factor), ET‐1 (endothelin 1), IL‐8 (interleukin 8), TGF‐β1 and TGF‐β2 (transforming growth factor‐beta 1 and 2) and VEGF‐A (vascular endothelial growth factor A) – using enzyme‐linked immunosorbent assays. We measured them from 71 Finnish wet AMD patients who were receiving intravitreal anti‐VEGF‐A injection treatments, as well as 64 age‐adjusted controls. Results We found significantly elevated levels of ET‐1, IL‐8 and TGF‐β2 in the serums of wet AMD patients. Conclusions ET‐1, IL‐8 and TGF‐β2 appear to be useful serum biomarkers in understanding active wet AMD. However, we cannot conclude that local retinal EMT‐processes could be observed from the corresponding systemic serum biomarkers in patients undergoing anti‐VEGF‐A treatments.

Type of Medium: Online Resource

ISSN: 1755-375X , 1755-3768

URL: Issue

URL: Article

DOI: 10.1111/aos.v100.5

DOI: 10.1111/aos.15051

Language: English

Publisher: Wiley

Publication Date: 2022

detail.hit.zdb_id: 2466981-7

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Psychiatric disorders are a common prognostic marker for worse outcome in patients with idiopathic intracranial hypertension

Puustinen, Tero ; Tervonen, Joona ; Avellan, Cecilia ; [et al.]

Elsevier BV ; 2019

In: Clinical Neurology and Neurosurgery Vol. 186 ( 2019-11), p. 105527-

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In: Clinical Neurology and Neurosurgery, Elsevier BV, Vol. 186 ( 2019-11), p. 105527-

Type of Medium: Online Resource

ISSN: 0303-8467

URL: Article

DOI: 10.1016/j.clineuro.2019.105527

Language: English

Publisher: Elsevier BV

Publication Date: 2019

detail.hit.zdb_id: 2004613-3

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Cerebrospinal fluid dynamics in idiopathic intracranial hypertension: a literature review and validation of contemporary findings

Kaipainen, Aku L ; Martoma, Erik ; Puustinen, Tero ; [et al.]

Springer Science and Business Media LLC ; 2021

In: Acta Neurochirurgica Vol. 163, No. 12 ( 2021-12), p. 3353-3368

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In: Acta Neurochirurgica, Springer Science and Business Media LLC, Vol. 163, No. 12 ( 2021-12), p. 3353-3368

Abstract: Idiopathic intracranial hypertension (IIH) is a rare disease of unknown aetiology related possibly to disturbed cerebrospinal fluid (CSF) dynamics and characterised by elevated intracranial pressure (ICP) causing optic nerve atrophy if not timely treated. We studied CSF dynamics of the IIH patients based on the available literature and our well-defined cohort. Method A literature review was performed from PubMed between 1980 and 2020 in compliance with the PRISMA guideline. Our study includes 59 patients with clinical, demographical, neuro-ophthalmological, radiological, outcome data, and lumbar CSF pressure measurements for suspicion of IIH; 39 patients had verified IIH while 20 patients did not according to Friedman’s criteria, hence referred to as symptomatic controls. Results The literature review yielded 19 suitable studies; 452 IIH patients and 264 controls had undergone intraventricular or lumbar CSF pressure measurements. In our study, the mean CSF pressure, pulse amplitudes, power of respiratory waves (RESP), and the pressure constant (P 0 ) were higher in IIH than symptomatic controls ( p 〈 0.01). The mean CSF pressure was higher in IIH patients with psychiatric comorbidity than without ( p 〈 0.05). In IIH patients without acetazolamide treatment, the RAP index and power of slow waves were also higher ( p 〈 0.05). IIH patients with excess CSF around the optic nerves had lower relative pulse pressure coefficient (RPPC) and RESP than those without ( p 〈 0.05). Conclusions Our literature review revealed increased CSF pressure, resistance to CSF outflow and sagittal sinus pressure (SSP) as key findings in IIH. Our study confirmed significantly higher lumbar CSF pressure and increased CSF pressure waves and RAP index in IIH when excluding patients with acetazolamide treatment. In overall, the findings reflect decreased craniospinal compliance and potentially depleted cerebral autoregulation resulting from the increased CSF pressure in IIH. The increased slow waves in patients without acetazolamide may indicate issues in autoregulation, while increased P 0 could reflect the increased SSP.

Type of Medium: Online Resource

ISSN: 0001-6268 , 0942-0940

URL: Article

DOI: 10.1007/s00701-021-04940-x

RVK:

XA 10000

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XA 12300

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 1464215-3

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Inflammation and its role in age-related macular degeneration

Kauppinen, Anu ; Paterno, Jussi J. ; Blasiak, Janusz ; [et al.]

Springer Science and Business Media LLC ; 2016

In: Cellular and Molecular Life Sciences Vol. 73, No. 9 ( 2016-5), p. 1765-1786

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In: Cellular and Molecular Life Sciences, Springer Science and Business Media LLC, Vol. 73, No. 9 ( 2016-5), p. 1765-1786

Type of Medium: Online Resource

ISSN: 1420-682X , 1420-9071

URL: Article

DOI: 10.1007/s00018-016-2147-8

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2016

detail.hit.zdb_id: 1458497-9

SSG: 12

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Mitophagy in the Retinal Pigment Epithelium of Dry Age-Related Macular Degeneration Investigated in the NFE2L2/PGC-1α-/- Mouse Model

Sridevi Gurubaran, Iswariyaraja ; Viiri, Johanna ; Koskela, Ali ; [et al.]

MDPI AG ; 2020

In: International Journal of Molecular Sciences Vol. 21, No. 6 ( 2020-03-13), p. 1976-

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In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 6 ( 2020-03-13), p. 1976-

Abstract: Increased oxidative stress and mitochondrial damage are observed in protein aggregation diseases, such as age-related macular degeneration (AMD). We have recently reported elevated levels of oxidative stress markers, damaged mitochondria, accumulating lysosomal lipofuscin and extracellular drusen-like structures in the retinal pigment epithelial cells (RPE) of the dry AMD-resembling NFE2L2/PGC1α double knockout (dKO) mouse model. Here, we provide evidence of a disturbance in the autolysosomal machinery handling mitochondrial clearance in the RPE cells of one-year-old NFE2L2/PGC1α-deficient mice. Confocal immunohistochemical analysis revealed an upregulation of autophagosome marker microtubule-associated proteins 1A/1B light chain 3B (LC3B) as well as numerous mitophagy markers, such as PTE-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase (PARKIN) together with damaged mitochondria. However, we detected no evidence of increased autolysosome formation in transmission electron micrographs or of colocalization of lysosomal marker LAMP2 (lysosome-associated membrane protein 2) and the mitochondrial marker ATP synthase β in confocal micrographs. Interestingly, we observed an upregulation of late autolysosomal fusion Ras-related protein (Rab7) in the perinuclear space of RPE cells together with autofluorescence aggregates. Our results reveal that there is at least a relative decrease of mitophagy in the RPE cells of NFE2L2/PGC1α dKO mice. This further supports the hypothesis that mitophagy is a putative therapy target in AMD-like pathology.

Type of Medium: Online Resource

ISSN: 1422-0067

URL: Article

DOI: 10.3390/ijms21061976

Language: English

Publisher: MDPI AG

Publication Date: 2020

detail.hit.zdb_id: 2019364-6

SSG: 12

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Autophagy Genes for Wet Age-Related Macular Degeneration in a Finnish Case-Control Study

Paterno, Jussi J. ; Koskela, Ali ; Hyttinen, Juha M.T. ; [et al.]

MDPI AG ; 2020

In: Genes Vol. 11, No. 11 ( 2020-11-06), p. 1318-

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In: Genes, MDPI AG, Vol. 11, No. 11 ( 2020-11-06), p. 1318-

Abstract: Age-related macular degeneration is an eye disease that is the main cause of legal blindness in the elderly in developed countries. Despite this, its pathogenesis is not completely known, and many genetic, epigenetic, environmental and lifestyle factors may be involved. Vision loss in age-related macular degeneration (AMD) is usually consequence of the occurrence of its wet (neovascular) form that is targeted in the clinic by anti-VEGF (vascular endothelial growth factor) treatment. The wet form of AMD is associated with the accumulation of cellular waste in the retinal pigment epithelium, which is removed by autophagy and the proteosomal degradation system. In the present work, we searched for the association between genotypes and alleles of single nucleotide polymorphisms (SNPs) of autophagy-related genes and wet AMD occurrence in a cohort of Finnish patients undergoing anti-VEGF therapy and controls. Additionally, the correlation between treatment efficacy and genotypes was investigated. Overall, 225 wet AMD patients and 161 controls were enrolled in this study. Ten SNPs (rs2295080, rs11121704, rs1057079, rs1064261, rs573775, rs11246867, rs3088051, rs10902469, rs73105013, rs10277) in the mTOR (Mechanistic Target of Rapamycin), ATG5 (Autophagy Related 5), ULK1 (Unc-51-Like Autophagy Activating Kinase 1), MAP1LC3A (Microtubule Associated Protein 1 Light Chain 3 α), SQSTM1 (Sequestosome 1) were analyzed with RT-PCR-based genotyping. The genotype/alleles rs2295080-G, rs11121704-C, rs1057079-C and rs73105013-T associated with an increased, whereas rs2295080-TT, rs2295080-T, rs11121704-TT, rs1057079-TT, rs1057079-T, rs573775-AA and rs73105013-C with a decreased occurrence of wet AMD. In addition, the rs2295080-GG, rs2295080-GT, rs1057079-TT, rs11246867-AG, rs3088051-CC and rs10277-CC genotypes were a positively correlated cumulative number of anti-VEGF injections in 2 years. Therefore, variability in autophagy genes may have an impact on the risk of wet AMD occurrence and the efficacy of anti-VEGF treatment.

Type of Medium: Online Resource

ISSN: 2073-4425

URL: Article

DOI: 10.3390/genes11111318

Language: English

Publisher: MDPI AG

Publication Date: 2020

detail.hit.zdb_id: 2527218-4

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Depletion of the Third Complement Component Ameliorates Age‐Dependent Oxidative Stress and Positively Modulates Autophagic Activity in Aged Retinas in a Mouse Model

Rogińska, Dorota ; Kawa, Miłosz P. ; Pius-Sadowska, Ewa ; [et al.]

Wiley ; 2017

In: Oxidative Medicine and Cellular Longevity Vol. 2017, No. 1 ( 2017-01)

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In: Oxidative Medicine and Cellular Longevity, Wiley, Vol. 2017, No. 1 ( 2017-01)

Abstract: The aim of the study was to investigate the influence of complement component C3 global depletion on the biological structure and function of the aged retina. In vivo morphology (OCT), electrophysiological function (ERG), and the expression of selected oxidative stress‐, apoptosis‐, and autophagy‐related proteins were assessed in retinas of 12‐month‐old C3‐deficient and WT mice. Moreover, global gene expression in retinas was analyzed by RNA arrays. We found that the absence of active C3 was associated with (1) alleviation of the age‐dependent decrease in retinal thickness and gradual deterioration of retinal bioelectrical function, (2) significantly higher levels of antioxidant enzymes (catalase and glutathione reductase) and the antiapoptotic survivin and Mcl‐1/Bak dimer, (3) lower expression of the cellular oxidative stress marker—4HNE—and decreased activity of proapoptotic caspase‐3, (4) ameliorated retinal autophagic activity with localization of ubiquitinated protein conjugates commonly along the retinal pigment epithelium (RPE) layer, and (5) significantly increased expression of several gene sets associated with maintenance of the physiological functions of the neural retina. Our findings shed light on mechanisms of age‐related retinal alterations by identifying C3 as a potential therapeutic target for retinal aging.

Type of Medium: Online Resource

ISSN: 1942-0900 , 1942-0994

URL: Issue

URL: Article

DOI: 10.1155/omcl.v2017.1

DOI: 10.1155/2017/5306790

Language: English

Publisher: Wiley

Publication Date: 2017

detail.hit.zdb_id: 2455981-7

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Pinosylvin Extract Retinari™ Sustains Electrophysiological Function, Prevents Thinning of Retina, and Enhances Cellular Response to Oxidative Stress in NFE2L2 Knockout Mice

Tamminen, Toni ; Koskela, Ali ; Toropainen, Elisa ; [et al.]

Hindawi Limited ; 2021

In: Oxidative Medicine and Cellular Longevity Vol. 2021 ( 2021-12-7), p. 1-16

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In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2021 ( 2021-12-7), p. 1-16

Abstract: Chronic oxidative stress eventually leads to protein aggregation in combination with impaired autophagy, which has been observed in age-related macular degeneration. We have previously shown an effective age-related macular degeneration disease model in mice with nuclear factor-erythroid 2-related factor-2 (NFE2L2) knockout. We have also shown pinosylvin, a polyphenol abundant in bark waste, to increase human retinal pigment epithelium cell viability in vitro. In this work, the effects of commercial natural pinosylvin extract, Retinari™, were studied on the electroretinogram, optical coherence tomogram, autophagic activity, antioxidant capacity, and inflammation markers. Wild-type and NFE2L2 knockout mice were raised until the age of 14.8 ± 3.8 months. They were fed with either regular or Retinari™ chow ( 141 ± 17.0 mg/kg/day of pinosylvin) for 10 weeks before the assays. Retinari™ treatment preserved significant retinal function with significantly preserved a- and b-wave amplitudes in the electroretinogram responses. Additionally, the treatment prevented thinning of the retina in the NFE2L2 knockout mice. The NFE2L2 knockout mice showed reduced ubiquitin-tagged protein accumulation in addition to local upregulation of complement factor H and antioxidant enzymes superoxide dismutase 1 and catalase. Therefore, the treatment in the NFE2L2 KO disease model led to reduced chronic oxidative stress and sustained retinal function and morphology. Our results demonstrate that pinosylvin supplementation could potentially lower the risk of age-related macular degeneration onset and slow down its progression.

Type of Medium: Online Resource

ISSN: 1942-0994 , 1942-0900

URL: Article

DOI: 10.1155/2021/8028427

Language: English

Publisher: Hindawi Limited

Publication Date: 2021

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Should we avoid colleagues in leisure time during the coronavirus disease 2019 (COVID-19) pandemic?

Oksanen, Lotta-Maria A. H. ; Sanmark, Enni ; Oksanen, Sampo A. ; [et al.]

Cambridge University Press (CUP) ; 2021

In: Infection Control & Hospital Epidemiology Vol. 42, No. 11 ( 2021-11), p. 1413-1414

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In: Infection Control & Hospital Epidemiology, Cambridge University Press (CUP), Vol. 42, No. 11 ( 2021-11), p. 1413-1414

Type of Medium: Online Resource

ISSN: 0899-823X , 1559-6834

URL: Article

DOI: 10.1017/ice.2020.1320

Language: English

Publisher: Cambridge University Press (CUP)

Publication Date: 2021

detail.hit.zdb_id: 2106319-9

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Detection improvement of gliomas in hyperspectral imaging of protoporphyrin IX fluorescence – in vitro comparison of visual identification and machine thresholds

Lehtonen, Samu J.R. ; Vrzakova, Hana ; Paterno, Jussi J. ; [et al.]

Elsevier BV ; 2022

In: Cancer Treatment and Research Communications Vol. 32 ( 2022), p. 100615-

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In: Cancer Treatment and Research Communications, Elsevier BV, Vol. 32 ( 2022), p. 100615-

Type of Medium: Online Resource

ISSN: 2468-2942

URL: Article

DOI: 10.1016/j.ctarc.2022.100615

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 2866646-X

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Berlin Brandenburg