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Mesenchymal stem cells (MSCs) represent a population of adult stem cells that have potent immunoregulatory, anti-inflammatory, and antiapoptotic properties. In addition, they have ability to migrate to the site of inflammation or injury, where they contribute to the regeneration and healing process. For these properties, MSCs have been used as therapeutic cells in several models, including treatment of damages or disorders of the ocular surface. If the damage of the ocular surface is extensive and involves a limbal region where limbal stem cell reside, MSC therapy has been proved as the effective treatment approach. Although the anti-inflammatory properties of MSCs have been well characterized, mechanisms of antiapoptotic action of MSCs are not well recognized. Using a chemically damaged cornea in a mouse model, we showed that the injury decreases expression of the gene for antiapoptotic molecule Bcl-2 and increases the expression of proapoptotic genes Bax and p53. These changes were attenuated by local transplantation of MSCs after corneal damage. The antiapoptotic effect of MSCs was tested in an in vitro model of co-cultivation of corneal explants with MSCs. The apoptosis of corneal cells in the explants was induced by proinflammatory cytokines and was significantly inhibited in the presence of MSCs. The antiapoptotic effect of MSCs was mediated by paracrine action, as confirmed by separation of the explants in inserts or by supernatants from MSCs. In addition, MSCs decreased the expression of genes for the molecules associated with endoplasmic reticulum stress Atf4, Bip, and p21, which are associated with apoptosis. The results show that MSCs inhibit the expression of proapoptotic genes and decrease the number of apoptotic cells in the damaged corneas, and this action might be one of the mechanisms of the therapeutic action of MSCs.

Článek

Brittle cornea syndrome: Disease-causing mutations in ZNF469 and two novel variants identified in a patient followed for 26 years

Biomedical papers of the Medical Faculty of the University Palacký, Olomouc Czech Republic. 2020 ; 164 (2) : 183-188. [pub] 20190417

Biomed. Pap. Fac. Med. Palacký Univ. Olomouc Czech Repub. (Print)
ISSN 1213-8118
Medvik
Zdroj

AIMS: Brittle cornea syndrome (BCS) is a rare autosomal recessive disorder. The aim of this study was to review ZNF469 mutations associated with BCS type 1 to date and to describe an additional case of Czech/Polish background. METHODS: Whole genome sequencing was undertaken to identify the molecular genetic cause of disease in the proband. Sequence variants in ZNF469 previously reported as BCS type 1-causing were searched in the literature, manually curated and aligned to the reference sequence NM_001127464.2. RESULTS: The proband has been reviewed since childhood with progressive myopia and hearing loss. Aged 13 years had been diagnosed with Stickler syndrome. Aged 16.5 years, he developed acute hydrops in the left eye managed by corneal transplantation. At the age of 26, he experienced right corneal rupture after blunt trauma, also managed by grafting. He had a number of secondary complications and despite regular follow-up and timely management, the right eye became totally blind and the left eye had light perception at the last follow-up visit, aged 42. He was found to be a compound heterozygote for two novel mutations c.1705C>T; p.(Gln569*) and c.1402_1411del; p.(Pro468Alafs*31) in ZNF469. In total 22 disease-causing variants in ZNF469 have been identified, mainly in consanguineous families or endogamous populations. Only four probands, including the case described in the current study, harboured compound heterozygous mutations. CONCLUSION: BCS occurs very rarely in outbred populations which may cause diagnostic errors due to poor awareness of the disease. Investigation into the underlying molecular genetic cause in patients with connective tissue disorders may lead to a re-evaluation of their clinical diagnosis.

MeSH
abnormality očí diagnóza genetika patofyziologie MeSH
artritida diagnóza MeSH
chybná diagnóza MeSH
dospělí MeSH
edém rohovky patofyziologie chirurgie MeSH
glaukom patofyziologie chirurgie MeSH
heterozygot MeSH
keratoplastika perforující MeSH
kožní abnormality diagnóza genetika patofyziologie MeSH
lidé MeSH
myopie patofyziologie MeSH
nemoci pojiva diagnóza MeSH
nestabilita kloubu vrozené diagnóza genetika patofyziologie MeSH
odchlípení sítnice diagnóza patofyziologie chirurgie MeSH
percepční nedoslýchavost diagnóza MeSH
perforace rohovky patofyziologie chirurgie MeSH
reoperace MeSH
trabekulektomie MeSH
transkripční faktory genetika MeSH
vitrektomie MeSH
Check Tag
dospělí MeSH
lidé MeSH
mužské pohlaví MeSH
Publikační typ
časopisecké články MeSH
kazuistiky MeSH
přehledy MeSH

Článek

Poranění rohovky
[Injury of cornea]

Míková, Lucie
Autor Míková, Lucie Veterinární klinika Vltava

Veterinární lékař. 2019 ; 17 (3) : 151-157.

ISSN 1214-3774
Medvik
Zdroj

Článek

The Healing of Oxidative Injuries with Trehalose in UVB-Irradiated Rabbit Corneas

Oxidative medicine and cellular longevity. 2019 ; 2019 (-) : 1857086. [pub] 20190919

Oxid Med Cell Longev
ISSN 1942-0994
Medvik
Zdroj

Our previous research revealed that trehalose, a nonreducing disaccharide of glucose and an important stress responsive factor, proved to have anti-inflammatory, antiapoptotic, and particularly antioxidant properties in UVB-irradiated corneas. Trehalose reduced oxidative stress in corneas induced by UVB irradiation, by means of a decrease in the antioxidant/prooxidant imbalance in the corneal epithelium. In this study, we demonstrate that trehalose of 3% or 6% concentration in eye drops directly decreases oxidative stress in UVB-irradiated corneas, by removing the excessive amount of reactive oxygen species (ROS). Trehalose drops applied on corneas during UVB irradiation once daily for four days resulted in a reduction or even absence of the oxidative stress, DNA damage, and peroxynitrite formation (detected by nitrotyrosine residues), seen in buffer-treated corneas. Furthermore, trehalose treatment applied curatively after repeated irradiation for the subsequent fourteen days led to the renewal of corneal transparency and significant suppression or even absence of neovascularization. This was in contrast to buffer-treated irradiated corneas, where the intracorneal inflammation was developed and the untransparent corneas were vascularized. In conclusion, the treatment of UVB-irradiated corneas with trehalose eye drops removed the excessive amount of ROS in the corneal epithelium, leading to the suppression of oxidative stress and favorable corneal healing. The 6% trehalose showed a higher intensive antioxidant effect.

Článek

Onemocnění rohovky [Corneal diseases]

Štěpánek Zavadilová, Tereza
Autor Autorita Veterinární nemocnice Libuš, Praha Veterinární klinika Jaggy, Praha

Veterinární lékař. 2018 ; 16 (2) : 109-112.

ISSN 1214-3774
Medvik
Zdroj

Článek

Endothelial Wound Repair of the Organ-Cultured Porcine Corneas

Current eye research. 2018 ; 43 (7) : 856-865. [pub] 20180413

Curr Eye Res
ISSN 1460-2202
Medvik
Zdroj

PURPOSE: To assess whether injured porcine endothelium of small and large corneoscleral disc differ in its reparative/regenerative capacity under various conditions of organ culture storage. MATERIAL AND METHODS: 166 paired porcine corneas were trephined to obtain tissues with diameter 12.0 mm and 17.5 mm (with area neighboring endothelial periphery). In tested discs, central endothelium was mechanically wounded. Density of live endothelial cells (LECD), percentage of dead cells (%DC), coefficient of variation and cell hexagonality were assessed in central and paracentral endothelium following 5- or 9-day incubation in medium with 2% or 10% fetal bovine serum. The parameters were assessed also in fresh and intact cultured discs. Dead endothelial cells (EC) were visualized by trypan blue, cell borders by Alizarin Red S dye. Endothelial imprints were immunoassayed for the proliferation marker Ki-67 and the nucleolar marker fibrillarin. RESULTS: In fresh corneas, the LECD/mm2 (mean ± standard deviation) were 3998.0 ± 215.4 (central area) and 3888.2 ± 363.1 (paracentral area). Only the length of storage had significant effect on wound repair. Lesion was repaired partially after 5-day and fully after 9-day cultivation. After 9-day storage in medium with 10% serum, the mean LECD detected in small discs were 2409.4 ± 881.8 (central area) and 3949.5 ± 275.5 (paracentral area) and in large discs the mean LECD were 2555.0 ± 347.0 (central area) and 4007.5 ± 261.2 (paracentral area). Ki-67 showed cell proliferation associated with healing of EC of both large and small corneas. CONCLUSIONS: The lesions were completely repaired within 9 days of storage. Presence of the area, where stem cells appear to be located, contributes to stimulation of endothelial reparation less than serum concentration and time of culture. Both cell migration and proliferation contribute to the wound repair.

MeSH
hojení ran fyziologie MeSH
modely nemocí na zvířatech MeSH
orgánové kultury - kultivační techniky MeSH
počet buněk MeSH
pohyb buněk MeSH
poranění rohovky patologie terapie MeSH
prasata MeSH
rohovkový endotel zranění patologie MeSH
tupá poranění patologie terapie MeSH
zvířata MeSH
Check Tag
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH

Článek

[RETRACTED] Therapeutic effect of molecular hydrogen in corneal UVB-induced oxidative stress and corneal photodamage

Scientific reports. 2017 ; 7 (1) : 18017. [pub] 20171221

Sci Rep
ISSN 2045-2322
Medvik
Zdroj

The aim of this study is to examine whether molecular hydrogen (H2) is able to reduce oxidative stress after corneal damage induced by UVB irradiation. We previously found that UVB irradiation of the cornea caused the imbalance between the antioxidant and prooxidant enzymes in the corneal epithelium, followed by the imbalance between metalloproteinases and their physiological inhibitors (imbalances in favour of prooxidants and metalloproteinases) contributing to oxidative stress and development of the intracorneal inflammation. Here we investigate the effect of H2 dissolved in PBS in the concentration 0.5 ppm wt/vol, applied on rabbit corneas during UVB irradiation and healing (UVB doses 1.01 J/cm2 once daily for four days). Some irradiated corneas remained untreated or buffer treated. In these corneas the oxidative stress appeared, followed by the excessive inflammation. Malondiladehyde and peroxynitrite expressions were present. The corneas healed with scar formation and neovascularization. In contrast, in H2 treated irradiated corneas oxidative stress was suppressed and malondiladehyde and peroxynitrite expressions were absent. The corneas healed with the restoration of transparency. The study provides the first evidence of the role of H2 in prevention of oxidative and nitrosative stress in UVB irradiated corneas, which may represent a novel prophylactic approach to corneal photodamage.