doktorska disertacija
Xhevat Lumi (Author), Marko Hawlina (Mentor), Marko Hawlina (Thesis defence commission member), Damjan Glavač (Thesis defence commission member), Dušica Pahor (Thesis defence commission member), Tomaž Gračner (Thesis defence commission member), Ivan Krajnc (Thesis defence commission member), Damjan Glavač (Co-mentor)

Abstract

Proliferativna vitreoretinopatija (PVR) predstavlja rast membran na površini mrežnice ter med mrežnico in steklovino pri bolnikih z regmatogenim odstopom mrežnice. Je najbolj pogost razlog za neuspeh pri zdravljenju bolnikov z odstopom mrežnice. Zaradi PVR imajo ti bolniki tudi slabši funkcionalni izid zdravljenja. Klinične raziskave kažejo, da kljub uspešnemu anatomskem zdravljenju bolniki nepojasnjeno izgubljajo tako centralni kot tudi periferni vid. Zaradi prizadetosti centralnega dela mrežnice, rumene pege, se poslabšata tako vidna ostrina kot tudi barvni vid. Zaradi okvare ostalih delov mrežnice imajo ti bolniki začasne ali trajne izpade vidnega polja. Številni dejavniki na celični in molekularni ravni so odgovorni za poslabšanje vida pri teh bolnikih. Morfološke analize rumene pege, narejene s pomočjo optične koherenčne tomografije (OCT), so pokazale, da je osip notranjih in zunanjih segmentov fovealnih fotoreceptorjev značilen pojav pri bolnikih s slabo vidno funkcijo po odstopu mrežnice. Zadnja desetletja so bile objavljene številne raziskave, ki nakazujejo na vpletenost rastnih dejavnikov in citokinov v patogenezi PVR. Skupaj s hipotezo rastnih dejavnikov se je porodilo vprašanje o vplivu genetskih dejavnikov na proces celjenja ran in na pojav PVR. Določanje genetskih determinant v povezavi s PVR se je pričelo v zadnjih desetih letih. V do sedaj objavljenih raziskavah je že bila dokazana povezava med posameznimi polimorfizmi enega nukleotida v genih TGFB1, SMAD7, p53, MDM2 in TNF in PVR, ki pa je ozko omejena samo na nekaj evropskih populacij. V naši raziskavi smo se osredotočili na klinične in genetske dejavnike PVR. Vrednotili smo funkcionalne plati rehabilitacije vidne funkcije bolnikov kot tudi morfološke spremembe, ki vplivajo na končni izid kirurškega zdravljenja. Poleg funkcionalnih preiskav, kot so vidna ostrina, barvni vid in vidno polje, smo v naši raziskavi analizirali tudi s pomočjo OCT pridobljene morfološke parametre: centralno debelino mrežnice (CRT) in skupno prostornino rumene pege (TMV). Analizirali smo vidno ostrino, barvni vid, vidno polje, stopnjo PVR, število operacij, očesni tlak, CRT in TMV za vse bolnike skupaj in za vsako skupino posebej. Pri vseh bolnikih, vključenih v raziskavo, smo ugotavljali, ali stopnja PVR vpliva na končno vidno ostrino. Analizirali smo, ali je barvni vid povezan s končno vidno ostrino. Prav tako smo pod drobnogled vzeli vprašanje o morebitni povezavi CRT in TMV z vidno ostrino in barvnim vidom, saj številna poročila kažejo, da so subklinične morfološke spremembe v rumeni pegi pomemben dejavnik za funkcionalno rehabilitacijo bolnikov po odstopu mrežnice. V raziskavo smo vključili 191 bolnikov z odstopom mrežnice, ki smo jih razdelili v 2 skupini: 113 bolnikov, pri katerih se je pojavila PVR (PVR skupina), in 78 bolnikov brez PVR (kontrolna skupina). Bolniki iz PVR skupine so imeli slabšo povprečno preoperativno vidno ostrino (0,13) v primerjavi s kontrolno skupino (0,28). Statistično pomembna razlika med skupinami je bila tudi glede postoperativne vidne ostrine. Povprečna postoperativna vidna ostrina bolnikov s PVR je bila slabša kot pri ostalih bolnikih z odstopom mrežnice. Zaradi relativno omejenega števila preiskovancev smo za genetsko analizo in v namen doseganja praga za ugotavljanje statistično značilnih povezav raziskavo za posamezne gene razširili na 261 primerov. Naša raziskava je pokazala statistično pomembne razlike v porazdelitvi genotipov med bolniki s PVR in kontrolnimi bolniki pri SNP-jih znotraj ali v bližini genov IL6, TGFB1 in IL10. V tej raziskavi nismo ugotovili povezanosti med SNP-ji znotraj ali v bližini genov za CCL2, FGF2, IL1A, IL2, JAK3, LTA, p53, PDGFRA, SMAD7, in TNF ter PVR, s čimer nismo potrdili do sedaj dognanih povezav med SNP-ji in PVR. Primerjali smo tudi razporeditev genotipov med kontrolno skupino 96 slovenskih krvodajalcev in bolnikov iz PVR skupine pri 4 SNP-jih v genih IL1A, IL2, LTA ter TNF.

Keywords

rastni faktorji;citokini;genetski polimorfizem;dejavniki tveganja;patogeneza;vidna ostrina;barvni vid;izpad vidnega polja;

Data

Language: Slovenian
Year of publishing:
Typology: 2.08 - Doctoral Dissertation
Organization: UM MF - Faculty of Medicine
Publisher: X. Lumi]
UDC: 577.21:617.735(043.3)
COBISS: 290257664 Link will open in a new window
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Other data

Secondary language: English
Secondary title: Association of growth factors and cytokines gene polymorphism with proliferative vitreoretinopathy
Secondary abstract: Proliferative vitreoretinopathy (PVR) is defined as the growth and contraction of cellular membranes within the vitreous cavity and on both retinal surfaces in patients with the rhegmatogenous retinal detachment (RRD). It is the major complication following the retinal detachment surgery and also a leading cause of failure in the management of RRD. Numerous clinical studies have shown that despite the successful anatomical treatment of RRD these patients inexplicably lose both central as well as peripheral vision. The structural changes of the central part of the retina, the macula lutea, consequently lead to the deterioration of both the visual acuity and the color vision. Due to involvement of other parts of retina, these patients have a temporary or permanent visual field loss. Numerous factors on the cellular and molecular levels are responsible for the vision impairment in these patients. Morphological analysis of macula lutea using optical coherence tomography (OCT) showed the characteristic drop-out of internal and external segments of foveal photoreceptors in patients with poor visual function after treatment. In recent years the question whether genetic factors are those who play a key role in the PVR development has become topical. Together with the “growth factors hypothesis” there arises the question about the effect of genetic factors on the wound healing process and on the development of the PVR. Results of genetic research published during the last decade have shown a strong association between the genetic profile in genes for TGFB1, SMAD7, TNF locus, MDM2, and p53 with the development of the PVR in some of European populations. The aim of our study was to enlighten the PVR from the clinical as well as from the genetic point of view. We evaluated functional aspects of visual function rehabilitation in patients with PVR as well as morphological retinal changes that have an impact on the final outcome of surgical treatment. In addition to the functional tests such as the visual acuity, color vision and visual field in our study we also analyzed the morphological OCT parameters: the central retinal thickness (CRT) and the total macular volume (TMV). We analyzed the visual acuity, color vision, visual field, PVR stage, number of surgeries required in patients with and without the PVR, intraocular pressure, CRT and TMV for all patients and for each group separately. In all patients included in the study we tried to find whether the PVR stage has an impact on the final visual acuity. We also analyzed if the color vision correlates with the final visual acuity. Questions whether the CRT and the TMV are correlated to the postoperative visual acuity and color vision were also taken into consideration, as many reports suggest that the subclinical morphological changes in the macula lutea are an important factor determining functional rehabilitation of patients with RRD. We genotyped SNPs in genes of CCL2, FGF2, IL1A, IL2, IL6, IL10, JAK3, LTA, SMAD7, p53, TGFB1, TNF and PDGFRA. Due to the relatively small sample size and for the purpose of achieving the threshold for the detection of statistically significant associations for some of the genes we expanded the research to 261 cases. Our study showed a statistically significant difference of TGFB1 SNP rs1800471, IL6 SNP rs1800795, and IL10 SNP rs1800871 between Slovenian patients with and without PVR. Contrary to findings of other study groups, in this study we did not find a statistically significant association between the PVR and the SNPs of genes for CCL2, FGF2, IL1A, IL2, JAK3, LTA, p53, PDGFRA, SMAD7, and TNF. We also compared the distribution of genotypes in 96 Slovenian blood donors and in patients from the PVR group at 4 SNPs in genes of IL1A, IL2, LTA and TNF. The comparison showed that the distribution of genotypes for the IL1A SNP rs17561 and TNF SNP rs1800629 significantly differs between the groups.
Secondary keywords: Proliferativna vitreoretinopatija;Disertacije;Genetika;
URN: URN:SI:UM:
Type (COBISS): Dissertation
Thesis comment: Univ. v Mariboru, Medicinska fak.
Pages: 170 str.
ID: 9151498