The role of Plasminogen activator inhibitors in the corneal wound healing processes

A látásélesség tökéletes és végleges korrekciója társadalmunk egyre inkább előtérbe kerülő igénye, amely álom megvalósulását az excimer lézerrel végzett refraktív lézersebészeti beavatkozások jelenthetik napjainkban. Az excimer lézerkezelések után azonban, a technika jelentős fejlődése ellenére is, akár a látásélesség csökkenését okozó szövődmények, pl. sebgyógyulási zavar, alakulhatnak ki. Mai tudásunk szerint, a corneális sebgyógyulási folyamatokat két nagy rendszer szabályozza plazminogén aktivátorok és plazminogén aktivátor inhibitorok segítségével, mely rendszerek megfelelő működése elengedhetetlen a megfelelő corneális sebgyógyulás szempontjából. A két rendszer egyensúlyának felborulása elhúzódó, kóros sebgyógyulást idézhet elő. Ismert, hogy terhesség alatt a plazminogén aktivátorok és inhibitorok szintje a vérben jelentős mértékben változik, amely felvetette ezek könnybeli szintjének változását, normális arányuk felborulásának lehetőségét ezen időszakban. A fentiek alapján vizsgáltuk a plazminogén aktivátor inhibitor szint változását a könnyben fotorefraktív lézerkezeléseket követően és ezen inhibitor szintek változásának összehasonlítását elvégeztük fotorefraktív keratektómiát (PRK) és lézer in situ keratomileusist (LASIK) követően. Továbbá tanulmányoztuk a plazminogén aktivátor inhibitor-2 (PAI-2) szint változását terhes nők könnymintáiban, összehasonlítva ezen változásokat a vérmintákban mért értékekkel. Vizsgálataink során, a lézerkezeléseket követően egy esetben haze, öt esetben corneális opacifikáció volt detektálható, szignifikáns összefüggést a preoperatíven emelkedett PAI-2 szint és a corneális homály kialakulása között nem tudtunk igazolni. A PRK és LASIK PAI-2 preoperatív és a közvetlen posztoperatív eredményeit egymással összehasonlítva nem találtunk szignifikáns különbséget az eredmények között. Azonban mindkét lézerkezelés során minden esetben a közvetlen posztoperatív eredmények és a többi időpontban vett minták eredményei között kifejezett szignifikáns különbséget találtunk. Fenti eredményeink alapján úgy tűnik, hogy a vizsgált refraktív sebészeti eljárások corneális sebgyógyulási folyamatában közös enzimatikus kontroll válasz állhat. A terhes nők könnymintáinak PAI-2 szintje a terhességi korral nem korrelált, a könnymintákban mért értékek alapvetően konstansak maradtak a terhesség folyamán. A vér PAI-2 szintje a terhességi korral előrehaladva fokozatosan emelkedett. Nagy valószínűséggel terhesekben szemfelszíni betegségek vagy sebzés hiányában a könnyszintek függetlenek az enzimek vérszintjének változásától.The need for an ever more perfect correction of both congenital and acquired refractive defects has come more and more to the foreground in the past century. Out of these tendencies, one of the most developing segments is the refractive laser eye surgery method done with an excimer laser. However, despite the significant development of technology, even nowadays, after the now routine excimer laser treatments, adverse reactions causing impaired vision or the reduction of visual acuity may appear. Based on our current knowledge, corneal wound healing processes are controlled by two big systems with the help of plasminogen activators (PAs) and plasminogen activator inhibitors (PAIs). The correct operation of the above mentioned systems is inevitable for proper wound healing. The disturbance in the equilibrium of the two systems can result in pathological wound healing. Normal pregnancy is accompanied by the reduction of fibrinolytic activity and the growth of PAIs concentration in blood. In possession of the above mentioned results, we started to examine the changes in level of plasminogen activator inhibitor-2 (PAI-2) following the refractive laser surgeries and make comparisons following photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). In addition, we analyse the change of the PAI-2 level in the tear samples of pregnant women comparing the results to the values taken from the blood samples. After PRK we found that one eye was detectable with haze by the third month, and further 5 eyes were affected by corneal opacification. In this study we could not prove a significant connection between the preoperative elevated PAI-2 level and the development of corneal haze. We compared the PAI-2 results of PRK and LASIK in the preoperative and directly postoperative sample, but we could not find any significant difference between them. During both of these laser treatments there was a significant difference between the results taken directly after operation and in the other periods. The PAI-2 levels of pregnant women’s tear samples did not correlate with the pregnant age, the values measured in the tear samples remained essentially constant during pregnancy. The PAI-2 level of blood constantly increased with the development of pregnancy. In the absence of ocular surface diseases, wounding or surgical intervention, the tear levels are independent of the change in the blood level of enzyme.N

Thrombophilic screening in retinal artery occlusion patients

Valeria Nagy1, Lili Takacs1, Zita Steiber1, György Pfliegler2, Andras Berta11Department of Ophthalmology, 2Division of Rare Diseases, University of Debrecen Medical and Health Science Center, Debrecen, HungaryBackground: Retinal artery occlusion (RAO) is an ischemic vascular damage of the retina, which frequently leads to sudden, mostly irreversible loss of vision. In this study, blood thrombophilic factors as well as cardiovascular risk factors were investigated for their relevance to this pathology. Thrombophilic risk factors so far not evaluated were included in the study.Patients and methods: 28 RAO patients and 81 matched control subjects were examined. From blood samples, protein C, protein S, antithrombinopathy, and factor V (Leiden) mutation (FV), factor II gene polymorphism, factor VIII C level, plasminogen activity, lipoprotein(a) and fibrinogen levels, hyperhomocysteinemia and presence of anticardiolipin – antiphospholipid antibodies were investigated. Possibly relevant pathologies such as diabetes mellitus, hypertension, and ischemic heart disease were also registered. Statistical analysis by logistic regression was performed with 95% confidence intervals.Results: In the group of patients with RAO only the incidence of hypertension (OR: 3.33, 95% CI: 1.30–9.70, p = 0.014) as an average risk factor showed significant difference, but thrombophilic factors such as hyperfibrinogenemia (OR: 2.9, 95% CI: 1.29–6.57, p = 0.010) and the presence of FV (Leiden mutation) (OR: 3.9, 95% CI: 1.43–10.96, p = 0.008) increased the chances of developing this disease.Conclusions: Our results support the assumption that thrombophilia may contribute to the development of RAO besides vascular damage due to the presence of cardiovascular risk factors. Further studies are needed, however, to justify the possible use of secondary prophylaxis in form of anticoagulant/antiplatelet therapy.Keywords: retinal arterial occlusion, risk factors, thrombophili

Plasminogen Activator Activity in Tears of Pregnant Women

Plasminogen activator activity (PAA) in tears of pregnant women was investigated at various gestation times to assess the availability of plasminogen activator for aiding potential corneal wound healing processes during pregnancy.PAA was measured by a spectrophotometric method. The analysis used 91 tear samples from pregnant and non-pregnant women, supplemented with 10 additional tear PAA measurements from non-pregnant women obtained in a previous study.Tear levels of PAA in pregnant women formed a bimodal distribution. Either the tear PAA level was zero or non-zero during pregnancy. When non-zero, the tear PAA level was dissociated from gestation time and not different than non-pregnant and post-pregnant levels. The frequency of occurrence of zero level tear PAA increased with gestation: 16%, 17% and 46% had zero tear PAA in samples taken from women in the first, second and third trimester, respectively.Overall, of the tear samples taken from women during pregnancy, a total of 26% were at zero tear PAA. The remaining tear samples had non-zero tear PAA values throughout gestation equivalent to non-pregnant tear PAA values, suggesting local control of the source of PAA in tears. Given the importance of the plasminogen activator system in tears to wound healing in the cornea, and the high occurrence of zero tear PAA in our sample of pregnant women, elective corneal surgery would be contraindicated. If corneal surgery is nevertheless necessary, the tear PAA level would be worth checking and patients with low level should be closely observed during the postoperative period

Amnionmembrán-transzplantációval kezelt corneabetegségek

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Concurrence of chromosome 3 and 4 aberrations in human uveal melanoma

Uveal melanoma (UM) is the most common primary intraocular malignancy with a very poor prognosis. The most frequent chromosome aberration in UM is the monosomy of chromosome 3. Previously, we demonstrated that ~50% of UMs express type-I receptor for luteinizing hormone-releasing hormone (LH-RH-R). The gene encoding LH-RH-R is located in chromosome 4 (location: 4q21.2); however, the occurrence of numerical aberrations of chromosome 4 have never been studied in UM. In the present study, we investigated the abnormalities of chromosome 3 and 4, and the possible correlation between them, as well as with LH-RH-R expression. Forty-six specimens of UM were obtained after enucleation. Numerical aberrations of chromosome 3 and 4 were studied by fluorescence in situ hybridization (FISH). Chromosome 4 was detected in normal biparental disomy only in 14 (30%) samples; however, 32 cases (70%) showed more than 2 signals/nucleus. Monosomy of chromosome 3 could be found in 16 (35%) samples. In 6 specimens (13%), more than 2 copies of chromosome 3 were found, while normal biparental disomy was detected in 24 (52%) samples. Statistical analysis indicated a statistically significant (p<0.05) correlation between the copy number of chromosome 3 and 4. Moreover, moderate difference was revealed in the survival rate of the UM patients with various pathological profiles. No correlation was found between chromosome aberrations and LH-RH-R expression. Our results clearly demonstrate abnormalities in chromosome 3 and 4 and the incidence of the monosomy of chromosome 3 in human UM. In summary, our results provide new incite concerning the genetic background of this tumor. Our findings could contribute to a more precise determination of the prognosis of human UM and to the development of new therapeutic approaches to this malignancy

Cell density dependent stimulation of PAI-1 and hyaluronan synthesis by TGF-[béta] in orbital fibroblasts

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The targeted LHRH analog AEZS-108 alters expression of genes related to angiogenesis and development of metastasis in uveal melanoma

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Characteristics of Hyaluronan Synthesis Inhibition by 4-Methylumbelliferone in Orbital Fibroblasts

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