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  1. Article ; Online: Corneal Hysteresis, Intraocular Pressure, and Progression of Glaucoma

    Patrick Murtagh / Colm O’Brien

    Journal of Clinical Medicine, Vol 11, Iss 2895, p

    Time for a “Hyst-Oric” Change in Clinical Practice?

    2022  Volume 2895

    Abstract: It is known that as people age their tissues become less compliant and the ocular structures are no different. Corneal Hysteresis (CH) is a surrogate marker for ocular compliance. Low hysteresis values are associated with optic nerve damage and visual ... ...

    Abstract It is known that as people age their tissues become less compliant and the ocular structures are no different. Corneal Hysteresis (CH) is a surrogate marker for ocular compliance. Low hysteresis values are associated with optic nerve damage and visual field loss, the structural and functional components of glaucomatous optic neuropathy. Presently, a range of parameters are measured to monitor and stratify glaucoma, including intraocular pressure (IOP), central corneal thickness (CCT), optical coherence tomography (OCT) scans of the retinal nerve fibre layer (RNFL) and the ganglion cell layer (GCL), and subjective measurement such as visual fields. The purpose of this review is to summarise the current evidence that CH values area risk factor for the development of glaucoma and are a marker for its progression. The authors will explain what precisely CH is, how it can be measured, and the influence that medication and surgery can have on its value. CH is likely to play an integral role in glaucoma care and could potentially be incorporated synergistically with IOP, CCT, and visual field testing to establish risk stratification modelling and progression algorithms in glaucoma management in the future.
    Keywords corneal hysteresis ; corneal thickness ; glaucoma ; progression ; risk stratification ; Medicine ; R
    Subject code 600
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: p53 and Myofibroblast Apoptosis in Organ Fibrosis

    Kealan McElhinney / Mustapha Irnaten / Colm O’Brien

    International Journal of Molecular Sciences, Vol 24, Iss 6737, p

    2023  Volume 6737

    Abstract: Organ fibrosis represents a dysregulated, maladaptive wound repair response that results in progressive disruption of normal tissue architecture leading to detrimental deterioration in physiological function, and significant morbidity/mortality. Fibrosis ...

    Abstract Organ fibrosis represents a dysregulated, maladaptive wound repair response that results in progressive disruption of normal tissue architecture leading to detrimental deterioration in physiological function, and significant morbidity/mortality. Fibrosis is thought to contribute to nearly 50% of all deaths in the Western world with current treatment modalities effective in slowing disease progression but not effective in restoring organ function or reversing fibrotic changes. When physiological wound repair is complete, myofibroblasts are programmed to undergo cell death and self-clearance, however, in fibrosis there is a characteristic absence of myofibroblast apoptosis. It has been shown that in fibrosis, myofibroblasts adopt an apoptotic-resistant, highly proliferative phenotype leading to persistent myofibroblast activation and perpetuation of the fibrotic disease process. Recently, this pathological adaptation has been linked to dysregulated expression of tumour suppressor gene p53. In this review, we discuss p53 dysregulation and apoptotic failure in myofibroblasts and demonstrate its consistent link to fibrotic disease development in all types of organ fibrosis. An enhanced understanding of the role of p53 dysregulation and myofibroblast apoptosis may aid in future novel therapeutic and/or diagnostic strategies in organ fibrosis.
    Keywords fibrosis ; p53 ; apoptosis ; myofibroblast ; extracellular matrix ; glaucoma ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Role of Epithelial-to-Mesenchymal Transition of Retinal Pigment Epithelial Cells in Glaucoma Cupping

    Eabha O’Driscoll / Emily Hughes / Mustapha Irnaten / Markus Kuehn / Deborah Wallace / Colm O’Brien

    Journal of Clinical Medicine, Vol 12, Iss 2737, p

    2023  Volume 2737

    Abstract: Optic nerve head (ONH) cupping is a clinical feature of glaucoma associated with extracellular matrix (ECM) remodelling and lamina cribrosa (LC) fibrosis. Peripapillary atrophy (PPA) occurs commonly in glaucoma, and is characterised by the loss of ... ...

    Abstract Optic nerve head (ONH) cupping is a clinical feature of glaucoma associated with extracellular matrix (ECM) remodelling and lamina cribrosa (LC) fibrosis. Peripapillary atrophy (PPA) occurs commonly in glaucoma, and is characterised by the loss of retinal pigment epithelium (RPE) adjacent to the ONH. Under pro-fibrotic conditions, epithelial cells throughout the body can differentiate into fibroblast-like cells through epithelial-to-mesenchymal transition (EMT) and contribute to ECM fibrosis. This is investigated here in the context of glaucoma and PPA. Human-donor ONH sections were assessed for the presence of the RPE cell-specific marker RPE65 using immunofluorescence. We examined the EMT response of ARPE-19 cells to the following glaucoma-related stimuli: cyclic mechanical stretch, mechanical stiffness, transforming growth factor beta (TGFβ), and tumour necrosis factor alpha (TNFα). The gene expression was measured using the PCR of the epithelial tight junction marker zona occludens 1 (ZO-1) and the mesenchymal markers alpha smooth muscle actin (αSMA) and vimentin. A scratch assay was used to assess the ARPE-19 migration. Significant RPE-65 staining was demonstrated in the glaucomatous ONH. The cyclic stretching and substrate stiffness of the ARPE-19 cells caused a significant decrease in ZO-1 ( p = 0.04), and an increase in αSMA ( p = 0.04). The scratch assays demonstrated increased migration of ARPE19 in the presence of TNFα ( p = 0.02). Furthermore, ARPE-19 cells undergo an EMT-like transition (gain of αSMA, loss of ZO-1 and increased migration) in response to glaucomatous stimuli. This suggests that during PPA, RPE cells have the potential to migrate into the ONH and differentiate into fibroblast-like cells, contributing to glaucomatous ONH cupping.
    Keywords glaucoma ; peripapillary atrophy ; epithelial mesenchymal transition ; retinal pigment epithelium cell ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Intra-Cellular Calcium Signaling Pathways (PKC, RAS/RAF/MAPK, PI3K) in Lamina Cribrosa Cells in Glaucoma

    Mustapha Irnaten / Aisling Duff / Abbot Clark / Colm O’Brien

    Journal of Clinical Medicine, Vol 10, Iss 62, p

    2021  Volume 62

    Abstract: The lamina cribrosa (LC) is a key site of fibrotic damage in glaucomatous optic neuropathy and the precise mechanisms of LC change remain unclear. Elevated Ca 2+ is a major driver of fibrosis, and therefore intracellular Ca 2+ signaling pathways are ... ...

    Abstract The lamina cribrosa (LC) is a key site of fibrotic damage in glaucomatous optic neuropathy and the precise mechanisms of LC change remain unclear. Elevated Ca 2+ is a major driver of fibrosis, and therefore intracellular Ca 2+ signaling pathways are relevant glaucoma-related mechanisms that need to be studied. Protein kinase C (PKC), mitogen-activated MAPK kinases ( p 38 and p 42/44-MAPK), and the PI3K/mTOR axis are key Ca 2+ signal transducers in fibrosis and we therefore investigated their expression and activity in normal and glaucoma cultured LC cells. We show, using Western immune-blotting, that hyposmotic-induced cellular swelling activates PKCα, p 42/ p 44, and p 38 MAPKs, the activity is transient and biphasic as it peaks between 2 min and 10 min. The expression and activity of PKCα, p 38 and p 42/ p 44-MAPKs are significantly ( p < 0.05) increased in glaucoma LC cells at basal level, and at different time-points after hyposmotic stretch. We also found elevated mRNA expression of mRNA expression of PI3K, IP3R, mTOR, and CaMKII in glaucoma LC cells. This study has identified abnormalities in multiple calcium signaling pathways (PKCα, MAPK, PI3K) in glaucoma LC cells, which might have significant functional and therapeutic implications in optic nerve head (ONH) fibrosis and cupping in glaucoma.
    Keywords glaucoma ; lamina cribrosa ; fibrosis ; calcium ; PKCα ; p 38-MAPK ; Medicine ; R
    Subject code 333
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Ocular Blood Flow and Visual Function

    Goji Tomita / David Huang / Colm O’Brien / Ki Ho Park / Toru Nakazawa

    BioMed Research International, Vol

    2015  Volume 2015

    Keywords Medicine ; R
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Proteomics Strategy for Identifying Candidate Bioactive Proteins in Complex Mixtures

    Roisin O'Connor / Lorna M. Cryan / Kieran Wynne / Andreas de Stefani / Desmond Fitzgerald / Colm O'Brien / Gerard Cagney

    Journal of Biomedicine and Biotechnology, Vol

    Application to the Platelet Releasate

    2010  Volume 2010

    Abstract: Proteomic approaches have proven powerful at identifying large numbers of proteins, but there are fewer reports of functional characterization of proteins in biological tissues. Here, we describe an experimental approach that fractionates proteins ... ...

    Abstract Proteomic approaches have proven powerful at identifying large numbers of proteins, but there are fewer reports of functional characterization of proteins in biological tissues. Here, we describe an experimental approach that fractionates proteins released from human platelets, linking bioassay activity to identity. We used consecutive orthogonal separation platforms to ensure sensitive detection: (a) ion-exchange of intact proteins, (b) SDS-PAGE separation of ion-exchange fractions and (c) HPLC separation of tryptic digests coupled to electrospray tandem mass spectrometry. Migration of THP-1 monocytes in response to complete or fractionated platelet releasate was assessed and located to just one of the forty-nine ion-exchange fractions. Over 300 proteins were identified in the releasate, with a wide range of annotated biophysical and biochemical properties, in particular platelet activation, adhesion, and wound healing. The presence of PEDF and involucrin, two proteins not previously reported in platelet releasate, was confirmed by western blotting. Proteins identified within the fraction with monocyte promigratory activity and not in other inactive fractions included vimentin, PEDF, and TIMP-1. We conclude that this analytical platform is effective for the characterization of complex bioactive samples.
    Keywords Biotechnology ; TP248.13-248.65 ; Chemical technology ; TP1-1185 ; Technology ; T ; DOAJ:Biotechnology ; DOAJ:Life Sciences ; DOAJ:Biology and Life Sciences
    Language English
    Publishing date 2010-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  7. Article ; Online: Proteomics Strategy for Identifying Candidate Bioactive Proteins in Complex Mixtures

    Roisin O'Connor / Lorna M. Cryan / Kieran Wynne / Andreas de Stefani / Desmond Fitzgerald / Colm O'Brien / Gerard Cagney

    Journal of Biomedicine and Biotechnology, Vol

    Application to the Platelet Releasate

    2010  Volume 2010

    Keywords Biotechnology ; TP248.13-248.65 ; Medicine ; R
    Language English
    Publishing date 2010-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: The p53 codon 72 PRO/PRO genotype may be associated with initial central visual field defects in caucasians with primary open angle glaucoma.

    Janey L Wiggs / Alex W Hewitt / Bao Jian Fan / Dan Yi Wang / Dayse R Figueiredo Sena / Colm O'Brien / Anthony Realini / Jamie E Craig / David P Dimasi / David A Mackey / Jonathan L Haines / Louis R Pasquale

    PLoS ONE, Vol 7, Iss 9, p e

    2012  Volume 45613

    Abstract: Loss of vision in glaucoma is due to apoptotic retinal ganglion cell loss. While p53 modulates apoptosis, gene association studies between p53 variants and glaucoma have been inconsistent. In this study we evaluate the association between a p53 variant ... ...

    Abstract Loss of vision in glaucoma is due to apoptotic retinal ganglion cell loss. While p53 modulates apoptosis, gene association studies between p53 variants and glaucoma have been inconsistent. In this study we evaluate the association between a p53 variant functionally known to influence apoptosis (codon 72 Pro/Arg) and the subset of primary open angle glaucoma (POAG) patients with early loss of central visual field.Genotypes for the p53 codon 72 polymorphism (Pro/Arg) were obtained for 264 POAG patients and 400 controls from the U.S. and in replication studies for 308 POAG patients and 178 controls from Australia (GIST). The glaucoma patients were divided into two groups according to location of initial visual field defect (either paracentral or peripheral). All cases and controls were Caucasian with European ancestry.The p53-PRO/PRO genotype was more frequent in the U.S. POAG patients with early visual field defects in the paracentral regions compared with those in the peripheral regions or control group (p=2.7 × 10(-5)). We replicated this finding in the GIST cohort (p =7.3 × 10(-3), and in the pooled sample (p=6.6 × 10(-7)) and in a meta-analysis of both the US and GIST datasets (1.3 × 10(-6), OR 2.17 (1.58-2.98 for the PRO allele).These results suggest that the p53 codon 72 PRO/PRO genotype is potentially associated with early paracentral visual field defects in primary open-angle glaucoma patients.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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