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Imaging of Human Lens Capsules with Pseudoexfoliation Syndrome by Time of Flight Secondary Ion Mass Spectrometry (TOF-SIMS)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. (Per Söderberg)ORCID-id: 0000-0002-9938-2808
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Oftalmiatrik.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nyckelord [en]
PEX, cataract, lens capsule, time of flight secondary mass spectrometry (TOF-SIMS), imaging mass spectrometry (IMS), sphingolipids
Nationell ämneskategori
Oftalmologi
Forskningsämne
Oftalmiatrik; Kemi med inriktning mot analytisk kemi
Identifikatorer
URN: urn:nbn:se:uu:diva-260946OAI: oai:DiVA.org:uu-260946DiVA, id: diva2:848881
Forskningsfinansiär
Vetenskapsrådet, 621-2011-4423Tillgänglig från: 2015-08-26 Skapad: 2015-08-26 Senast uppdaterad: 2015-10-01
Ingår i avhandling
1. Molecular and epidemiological studies on eyes with pseudoexfoliation syndrome
Öppna denna publikation i ny flik eller fönster >>Molecular and epidemiological studies on eyes with pseudoexfoliation syndrome
2015 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Pseudoexfoliation (PEX) syndrome is an age-related condition characterized by the production and accumulation of extracellular fibrillary material in the anterior segment of the eye. PEX predisposes for several pathological conditions, such as glaucoma and complications during and after cataract surgery. The pathogenesis of PEX is not yet fully understood. It is multifactorial with genetics and ageing as contributing factors.

We aimed to study the proteome in aqueous humor (AH) in PEX in order to increase the knowledge about its pathophysiology. Therefore, we developed sampling techniques and evaluated separation methods necessary for analyzing small sample volumes. Other objectives were to study the lens capsule in eyes with PEX regarding small molecules, and to investigate the association between PEX and cataract surgery in a population-based 30-year follow-up study.

Samples of AH from eyes with PEX and control eyes were collected during cataract surgery. In pooled, and individual samples, various liquid based separation techniques and high resolution mass spectrometry were utilized. For quantitation, various methods for labeling, and label free techniques were applied. Lens capsules were collected from some of the patients, and analysed by imaging mass spectrometry. A cohort of 1,471 elderly individuals underwent a comprehensive ophthalmological examination at baseline. Medical information was obtained by questionnaires, and from medical records. Incident cases of cataract surgery were identified by review of medical records.

In the initial study, several techniques were explored for protein detection, and a number of proteins were identified as differentially expressed. In the individually labelled samples, changes in the proteome were observed. Eyes with PEX contained higher levels of proteins involved in inflammation, oxidative stress, and coagulation, suggesting that these mechanisms are involved in the pathogenesis in PEX. The levels of β/γ-crystallins were significantly increased in PEX, which is a novel finding. In the lens capsules from individuals with PEX, changes in the lipid composition was observed with time-of-flight secondary ion mass spectrometry. These changes remain to be elucidated. By multivariate analysis, lens opacities were the first, and PEX the second most important predictor for cataract surgery, the later accounting for a 2.38-fold increased risk for cataract surgery.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2015. s. 54
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1130
Nyckelord
Pseduoexfoliation syndrome, PEX, aqueous humor, cataract, cataract surgery, lens capsule, proteomics, mass spectrometry, MS, MALDI TOF MS/MS, quantitative proteomics, iTRAQ, dimethyl labeling, imaging mass spectrometry, IMS, time of flight secondary ion mass spectrometry, TOF-SIMS, crystallin, epidemiology, risk factor
Nationell ämneskategori
Oftalmologi
Forskningsämne
Oftalmiatrik
Identifikatorer
urn:nbn:se:uu:diva-260714 (URN)978-91-554-9312-7 (ISBN)
Disputation
2015-10-15, Fåhreussalen,ingång C5, Rudbecklaboratoriet, Akademiska sjukhuset, Dag Hammarskjölds väg 20, 751 85 Uppsala, Uppsala, 13:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2015-09-24 Skapad: 2015-08-24 Senast uppdaterad: 2015-10-01

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Botling Taube, Amelie

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Institutionen för neurovetenskapAnalytisk kemiOftalmiatrik
Oftalmologi

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