Title Glikozilacijski obrazac proteina u senilnoj makularnoj degeneraciji
Title (english) Glycosylation pattern of proteins across the age-related macular degeneration
Author Ivona Bućan
Mentor Ozren Polašek (mentor)
Committee member Ljubo Znaor (predsjednik povjerenstva)
Committee member Irena Drmić-Hofman (član povjerenstva)
Committee member Veljko Rogošić (član povjerenstva)
Granter University of Split School of Medicine Split
Defense date and country 2023-03-24, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Ophthalmology
Universal decimal classification (UDC ) 617 - Surgery. Orthopaedics. Ophthalmology
Abstract Senilna makularna degeneracija (SMD) bolest je centralnog dijela mrežnice. Vodeći je uzrok sljepoće u populaciji iznad 55 godina života i treći globalni uzrok sljepoće iza mrene i glaukoma. Brojna su istraživanja usmjerena na razumijevanje etiopatogeneze i pronalazak potencijalnih biomarkera. Glikozilacija je proces posttranslacijske modifikacije proteina. Imunoglobulini G (IgG) najbolje su proučeni N-glikoproteini koji sudjeluju u kontroliranom imunološkom odgovoru, a razlika u glikozilacijskom profilu IgG ovisi o genetičkoj i epigenetičkoj regulaciji, kao i konstitucijskim i okolišnim čimbenicima. Promjene glikozilacije nazočne su u ranoj akutnoj fazi i razvojem kroničnih stadija bolesti, pa bi analiza glikanskog profila proteina i imunoglobulina G u plazmi bila značajna u rasvjetljivanju mehanizama uključenih u patogenezu SMD-a. Cilj ovog istraživanja bio je ispitati promjene obrasca glikozilacije sveukupnih proteina i imunoglobulina G u plazmi, u različitim skupinama ispitanika s degenerativnim promjenama u makuli iz kohorte „10, 001 Dalmatinac” te ih usporediti s relevantnom kontrolnom skupinom. Ispitanici s jednostranim i obostranim znakovima senilne makularne degeneracije bili su starije životne dobi, s poremećenim metabolizmom lipida. Multivarijantnom analizom glikanskih struktura u ispitanika s makularnom degeneracijom mlađih od 55 godina nije dobiven statistički značajan rezultat. U ispitanika starije životne dobi s jednostranom prezentacijom senilne makularne degeneracije najznačajniji rezultat predstavljaju snižene razine digalaktoziliranih biantenarnih glikana sa sržnom fukozom i terminalno vezanom sijalnom kiselinom [IgG_GP18 (P < 0,009)], što upućuje na slom reparativnih mehanizama i poremećaj imunološke regulacije. U ispitanika s obostranim znakovima senilne makularne degeneracije najznačajniji rezultat predstavlja porast tetraantenarnih glikanskih struktura s fukozilacijom vanjske grane [DG13 (P < 0,001)], što odgovara promociji upalnog stanja u organizmu. Sve tri skupine ispitanika u jednoj kategoriji u odnosu na kontrolnu skupinu značajno su se razlikovale samo u porastu tetraantenarnih glikana s fukozilacijom vanjske grane. Takav rezultat otkriva nedostatke provedenog istraživanja u smislu poprečne prirode studije temeljene na jednostrukom mjerenju glikanskih struktura iz jednog dostupnog biološkog uzorka. Ustroj budućih studija trebao bi se temeljiti na preciznijoj procjeni i klasifikaciji ispitanika prema fenotipu bolesti, uz kontinuirano kliničko praćenje i višestruko mjerenje glikana iz različitih bioloških uzoraka.
Abstract (english) Age-related macular degeneration (AMD) is a disease of the central portion of the retina. It is the leading cause of blindness in over-55 population and the third cause of blindness globally, after cataracts and glaucoma. Numerous research projects are devoted to elucidating the etiopathogenesis and identifying potential biomarkers. Glycosylation is the post-translational modification process for proteins. Immunoglobulin G (IgG) is well-studied N-glycoprotein that participates in the homeostatic control of the immune response. The interindividual variation in the glycosylation profile of IgG is affected by the expression of glycan-related genes, epigenetic regulation, as well as constitutional and environmental factors. Glycosylation changes are present in the early acute phase and the development of chronic stages of the disease; therefore, the analysis of the glycan profile of proteins and immunoglobulin G in plasma would be significant in identifying the processes involved in the pathogenesis of AMD. The objective of this study was to compare the glycosylation patterns of total proteins and immunoglobulin G in plasma from different groups of 10,001 Dalmatian subjects with macula degeneration to a relevant control group. The subjects with unilateral and bilateral signs of AMD were elderly people and had dysfunctional lipid metabolism.The multivariate analysis of glycan structures did not produce a significant result in subjects under 55 years of age with macular degeneration. The most significant result regarded lower odds for di-galactylated bi-antennary glycans with core fucose and terminally attached sialic acid [IgG_GP18 (P < 0,009)] in unilateral cases of AMD. The described alterations in glycan structures may indicate a failure of reparative para-inflammatory mechanisms. The most significant result revealed increased odds for tetra-antennary structures with fucosylation of the outer branch grane [DG13 (P < 0,001)], which is a strong indicator of inflammation, in bilateral cases of AMD. Only the increase in tetra-antennary glycans with fucosylation of the outer branch was significantly different between the three subject groups in one category and the control group. This result reveals the limitations of the conducted research due to the cross-sectional nature of the study based on a single measurement of glycan structures from a single available biological sample. Future studies should aim for a more precise evaluation and classification of subjects according to disease phenotype, with continuous clinical monitoring and multiple measurements of glycans in various biological samples.
Keywords
senilna makularna degeneracija
glikozilacija
N-glikani
biomarker
Keywords (english)
age-related macular degeneration
glycosylation
N-glycans
biomarker
Language croatian
URN:NBN urn:nbn:hr:171:694744
Study programme Title: Translational Research in Biomedicine - TRIBE Study programme type: university Study level: postgraduate Academic / professional title: doktor/doktorica znanosti, interdisciplinarna područja znanosti (doktor/doktorica znanosti, interdisciplinarna područja znanosti)
Type of resource Text
File origin Born digital
Access conditions Open access
Terms of use
Created on 2023-03-24 08:20:46