Skip to main content
Erschienen in: International Ophthalmology 1/2019

13.01.2018 | Original Paper

Comparative evaluation of the aqueous humor proteome of primary angle closure and primary open angle glaucomas and age-related cataract eyes

Erschienen in: International Ophthalmology | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To analyze and compare the total proteome of aqueous humor (AH) from patients having primary angle closure glaucoma (PACG), primary open angle glaucoma (POAG) and age-related cataract.

Materials and methodology

Aqueous humor was collected from age-matched PACG, POAG and cataract patients who underwent surgery, and it was immediately stored at − 80 °C until analysis. From each sample, 25 µg of total protein was subjected to trypsin digestion and subsequently LC–MS/MS analysis was performed for the deep proteome analysis. The data acquired after the LC–MS/MS analysis were analyzed using Proteome Discoverer 1.4. The identified peptide matches were validated using percolator, at less than 1% false discovery rates.

Results

A total of 625, 594 and 636 proteins were identified in PACG, POAG and cataract groups, respectively (n = 9 in each group). The inter-group comparison among all these groups showed that 246 proteins were identified in all the three groups. An average of 236 ± 42, 218 ± 40 and 214 ± 62 proteins from each AH sample of PACG, POAG and cataract, respectively, was identified. There were 53 proteins commonly found in all 9 PACG AH, 59 proteins in POAG AH and 42 proteins in 9 cataracts AH samples. In the individual analysis, there were 28 proteins found in all the samples analyzed representing the “constitutive AH proteome.” Spectral counting analysis of 246 proteins identified in all three group types showed significant differences in protein abundance. In proteins unique to PACG AH, 7 proteins viz. ARHGEF12, APC2, WAS, PIK3CG, ITGB1, MSN and PFN1 out of 226 were found in “Regulation of Actin Cytoskeleton” pathway, whereas in POAG 5 out of 206 proteins viz. ADCY2, ITPR1, MAPK3, MAP3K2 and TUBB1 were found in “Gap Junction” pathway.

Conclusions

A qualitative as well as a quantitative comparison of proteomes of AH from PACG, POAG and age-related cataract eyes showed significant differences, thus providing clues to the disease pathophysiology.
Literatur
1.
Zurück zum Zitat Izzotti A, Bagnis A, Sacca SC (2011) The role of oxidative stress in glaucoma. Mutat Res 612:105–114CrossRef Izzotti A, Bagnis A, Sacca SC (2011) The role of oxidative stress in glaucoma. Mutat Res 612:105–114CrossRef
3.
Zurück zum Zitat Grieshaber MC, Mozaffarieh M, Flammer J (2007) What is the link between vascular dysregulation and glaucoma? Surv Ophthalmol 2:144–154CrossRef Grieshaber MC, Mozaffarieh M, Flammer J (2007) What is the link between vascular dysregulation and glaucoma? Surv Ophthalmol 2:144–154CrossRef
4.
Zurück zum Zitat Chowdhury UR, Madden BJ, Charlesworth MC, Fautsch MP (2010) Proteome analysis of human aqueous humor. Invest Ophthalmol Vis Sci 5:4921–4931CrossRef Chowdhury UR, Madden BJ, Charlesworth MC, Fautsch MP (2010) Proteome analysis of human aqueous humor. Invest Ophthalmol Vis Sci 5:4921–4931CrossRef
5.
Zurück zum Zitat Bennett KL, Funk M, Tschernutter M, Breitwieser FP, Planyavsky M, Ubaida MC, Muller A, Trajanoski Z, Colinge J, Superti-Furga G, Chmidt-Erfurth U (2011) Proteomic analysis of human cataract aqueous humour: comparison of one-dimensional gel LCMS with two-dimensional LCMS of unlabelled and iTRAQ®-labelled specimens. J Proteomics 74:151–166CrossRefPubMed Bennett KL, Funk M, Tschernutter M, Breitwieser FP, Planyavsky M, Ubaida MC, Muller A, Trajanoski Z, Colinge J, Superti-Furga G, Chmidt-Erfurth U (2011) Proteomic analysis of human cataract aqueous humour: comparison of one-dimensional gel LCMS with two-dimensional LCMS of unlabelled and iTRAQ®-labelled specimens. J Proteomics 74:151–166CrossRefPubMed
6.
Zurück zum Zitat Duan X, Lu Q, Xue P, Zhang H, Dong Z, Yang F, Wang N (2008) Proteomic analysis of aqueous humor from patients with myopia. Mol Vis 14:370–377PubMedPubMedCentral Duan X, Lu Q, Xue P, Zhang H, Dong Z, Yang F, Wang N (2008) Proteomic analysis of aqueous humor from patients with myopia. Mol Vis 14:370–377PubMedPubMedCentral
7.
Zurück zum Zitat Funding M, Vorum H, Honore B, Nexo E, Ehlers N (2005) Proteomic analysis of aqueous humour from patients with acute corneal rejection. Acta Ophthalmol Scand 83:31–39CrossRefPubMed Funding M, Vorum H, Honore B, Nexo E, Ehlers N (2005) Proteomic analysis of aqueous humour from patients with acute corneal rejection. Acta Ophthalmol Scand 83:31–39CrossRefPubMed
8.
Zurück zum Zitat Kim TW, Kang JW, Ahn J, Lee EK, Cho KC, Han BN, Hong NY, Park J, Kim KP (2012) Proteomic analysis of the aqueous humor in age-related macular degeneration (AMD) patients. J Proteome Res 11:4034–4043CrossRefPubMed Kim TW, Kang JW, Ahn J, Lee EK, Cho KC, Han BN, Hong NY, Park J, Kim KP (2012) Proteomic analysis of the aqueous humor in age-related macular degeneration (AMD) patients. J Proteome Res 11:4034–4043CrossRefPubMed
9.
Zurück zum Zitat Izzotti A, Longobardi M, Cartiglia C, Sacca SC (2010) Proteome alterations in primary open angle glaucoma aqueous humor. J Proteome Res 9:4831–4838CrossRefPubMed Izzotti A, Longobardi M, Cartiglia C, Sacca SC (2010) Proteome alterations in primary open angle glaucoma aqueous humor. J Proteome Res 9:4831–4838CrossRefPubMed
10.
Zurück zum Zitat Anshu A, Price MO, Richardson Segu ZM, Lai X, Yoder MC, Price FW (2011) Alterations in the aqueous humor proteome in patients with a glaucoma shunt device. Mol Vis 17:1891–1900PubMedPubMedCentral Anshu A, Price MO, Richardson Segu ZM, Lai X, Yoder MC, Price FW (2011) Alterations in the aqueous humor proteome in patients with a glaucoma shunt device. Mol Vis 17:1891–1900PubMedPubMedCentral
11.
Zurück zum Zitat Zybailov B, Coleman MK, Florens L, Washburn MP (2005) Correlation of relative abundance ratios derived from peptide ion chromatograms and spectrum counting for quantitative proteomic analysis using stable isotope labeling. Anal Chem 77:6218–6224CrossRefPubMed Zybailov B, Coleman MK, Florens L, Washburn MP (2005) Correlation of relative abundance ratios derived from peptide ion chromatograms and spectrum counting for quantitative proteomic analysis using stable isotope labeling. Anal Chem 77:6218–6224CrossRefPubMed
12.
Zurück zum Zitat Zybailov B, Mosley AL, Sardiu ME, Coleman MK, Florens L, Washburn MP (2006) Statistical analysis of membrane proteome expression changes in Saccharomyces cerevisiae. J Proteome Res 5:2339–2347CrossRefPubMed Zybailov B, Mosley AL, Sardiu ME, Coleman MK, Florens L, Washburn MP (2006) Statistical analysis of membrane proteome expression changes in Saccharomyces cerevisiae. J Proteome Res 5:2339–2347CrossRefPubMed
13.
Zurück zum Zitat Latarya G, Mansour A, Epstein I, Cotlear D, Pikkel J, Levartovsky S, Yulish M, Beit-Yannai E (2012) Human aqueous humor phosphatase activity in cataract and glaucoma. Invest Ophthalmol Vis Sci 53:1679–1684CrossRefPubMed Latarya G, Mansour A, Epstein I, Cotlear D, Pikkel J, Levartovsky S, Yulish M, Beit-Yannai E (2012) Human aqueous humor phosphatase activity in cataract and glaucoma. Invest Ophthalmol Vis Sci 53:1679–1684CrossRefPubMed
14.
Zurück zum Zitat Nga AD, Yap SL, Samsudin A, Abdul-Rahman PS, Hashim OH, Mimiwati Z (2014) Matrix metalloproteinases and tissue inhibitors of metalloproteinases in the aqueous humour of patients with primary angle closure glaucoma—a quantitative study. BMC Ophthalmol 14:33CrossRefPubMedPubMedCentral Nga AD, Yap SL, Samsudin A, Abdul-Rahman PS, Hashim OH, Mimiwati Z (2014) Matrix metalloproteinases and tissue inhibitors of metalloproteinases in the aqueous humour of patients with primary angle closure glaucoma—a quantitative study. BMC Ophthalmol 14:33CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Dan J, Belyea D, Gertner G, Leshem I, Lusky M, Miskin R (2005) Plasminogen activator inhibitor-1 in the aqueous humor of patients with and without glaucoma. Arch Ophthalmol 123:220–224CrossRefPubMed Dan J, Belyea D, Gertner G, Leshem I, Lusky M, Miskin R (2005) Plasminogen activator inhibitor-1 in the aqueous humor of patients with and without glaucoma. Arch Ophthalmol 123:220–224CrossRefPubMed
16.
Zurück zum Zitat Sacca SC, Centofanti M, Izzotti A (2012) New proteins as vascular biomarkers in primary open angle glaucomatous aqueous humor. Invest Ophthalmol Vis Sci 53:4242–4253CrossRefPubMed Sacca SC, Centofanti M, Izzotti A (2012) New proteins as vascular biomarkers in primary open angle glaucomatous aqueous humor. Invest Ophthalmol Vis Sci 53:4242–4253CrossRefPubMed
17.
Zurück zum Zitat Clark R, Nosie A, Walker T, Faralli JA, Filla MS, Barrett-Wilt G (2013) Comparative genomic and proteomic analysis of cytoskeletal changes in dexamethasone-treated trabecular meshwork cells. Mol Cell Proteomics 12:194–206CrossRefPubMed Clark R, Nosie A, Walker T, Faralli JA, Filla MS, Barrett-Wilt G (2013) Comparative genomic and proteomic analysis of cytoskeletal changes in dexamethasone-treated trabecular meshwork cells. Mol Cell Proteomics 12:194–206CrossRefPubMed
18.
Zurück zum Zitat Malone P, Miao H, Parker A, Juarez S, Hernandez MR (2007) Pressure induces loss of gap junction communication and redistribution of connexin 43 in astrocytes. Glia 55:1085–1098CrossRefPubMed Malone P, Miao H, Parker A, Juarez S, Hernandez MR (2007) Pressure induces loss of gap junction communication and redistribution of connexin 43 in astrocytes. Glia 55:1085–1098CrossRefPubMed
19.
Zurück zum Zitat Ferreira SM, Lerner SF, Brunzini R, Evelson PA, Llesuy SF (2004) Oxidative stress markers in aqueous humor of glaucoma patients. Am J Ophthalmol 137:62–69CrossRefPubMed Ferreira SM, Lerner SF, Brunzini R, Evelson PA, Llesuy SF (2004) Oxidative stress markers in aqueous humor of glaucoma patients. Am J Ophthalmol 137:62–69CrossRefPubMed
20.
Zurück zum Zitat Levkovitch-Verbin H (2015) Retinal ganglion cell apoptotic pathway in glaucoma: initiating and downstream mechanisms. Prog Brain Res 220:37–57CrossRefPubMed Levkovitch-Verbin H (2015) Retinal ganglion cell apoptotic pathway in glaucoma: initiating and downstream mechanisms. Prog Brain Res 220:37–57CrossRefPubMed
21.
Zurück zum Zitat Brandt SK, Weatherly ME, Ware L, Linn DM, Linn CL (2011) Calcium preconditioning triggers neuroprotection in retinal ganglion cells. Neuroscience 172:387–397CrossRefPubMed Brandt SK, Weatherly ME, Ware L, Linn DM, Linn CL (2011) Calcium preconditioning triggers neuroprotection in retinal ganglion cells. Neuroscience 172:387–397CrossRefPubMed
22.
Zurück zum Zitat Izzotti A, Sacca SC, Longobardi M, Cartiglia C (2010) Mitochondrial damage in the trabecular meshwork of patients with glaucoma. Arch Ophthalmol 128:724–730CrossRefPubMed Izzotti A, Sacca SC, Longobardi M, Cartiglia C (2010) Mitochondrial damage in the trabecular meshwork of patients with glaucoma. Arch Ophthalmol 128:724–730CrossRefPubMed
23.
Zurück zum Zitat Kaur I, Pillai MG, Singh N (2012) An overview of biologics: science behind protein therapeutics. J Proteins Proteomics 3:229–237 Kaur I, Pillai MG, Singh N (2012) An overview of biologics: science behind protein therapeutics. J Proteins Proteomics 3:229–237
24.
Zurück zum Zitat Maier P, Broszinski A, Heizmann U, Boehringer D, Reinhard T (2006) Determination of active TGF-beta2 in aqueous humor prior to and following cryopreservation. Mol Vis 12:1477–1482PubMed Maier P, Broszinski A, Heizmann U, Boehringer D, Reinhard T (2006) Determination of active TGF-beta2 in aqueous humor prior to and following cryopreservation. Mol Vis 12:1477–1482PubMed
25.
Zurück zum Zitat Agarwal P, Daher AM, Agarwal R (2015) Aqueous humor TGF-β2 levels in patients with open-angle glaucoma: a meta-analysis. Mol Vis 21:612–620PubMedPubMedCentral Agarwal P, Daher AM, Agarwal R (2015) Aqueous humor TGF-β2 levels in patients with open-angle glaucoma: a meta-analysis. Mol Vis 21:612–620PubMedPubMedCentral
26.
Zurück zum Zitat Escoffier P, Paris L, Bodaghi B, Danis M, Mazier D, Marinach-Patrice C (2010) Pooling aqueous humor samples: bias in 2D-LC-MS/MS strategy? J Proteome Res 9:789–797CrossRefPubMed Escoffier P, Paris L, Bodaghi B, Danis M, Mazier D, Marinach-Patrice C (2010) Pooling aqueous humor samples: bias in 2D-LC-MS/MS strategy? J Proteome Res 9:789–797CrossRefPubMed
Metadaten
Titel
Comparative evaluation of the aqueous humor proteome of primary angle closure and primary open angle glaucomas and age-related cataract eyes
Publikationsdatum
13.01.2018
Erschienen in
International Ophthalmology / Ausgabe 1/2019
Print ISSN: 0165-5701
Elektronische ISSN: 1573-2630
DOI
https://doi.org/10.1007/s10792-017-0791-0

Weitere Artikel der Ausgabe 1/2019

International Ophthalmology 1/2019 Zur Ausgabe

Neu im Fachgebiet Augenheilkunde

Ophthalmika in der Schwangerschaft

Die Verwendung von Ophthalmika in der Schwangerschaft und Stillzeit stellt immer eine Off-label-Anwendung dar. Ein Einsatz von Arzneimitteln muss daher besonders sorgfältig auf sein Risiko-Nutzen-Verhältnis bewertet werden. In der vorliegenden …

Operative Therapie und Keimnachweis bei endogener Endophthalmitis

Vitrektomie Originalie

Die endogene Endophthalmitis ist eine hämatogen fortgeleitete, bakterielle oder fungale Infektion, die über choroidale oder retinale Gefäße in den Augapfel eingeschwemmt wird [ 1 – 3 ]. Von dort infiltrieren die Keime in die Netzhaut, den …

Bakterielle endogene Endophthalmitis

Vitrektomie Leitthema

Eine endogene Endophthalmitis stellt einen ophthalmologischen Notfall dar, der umgehender Diagnostik und Therapie bedarf. Es sollte mit geeigneten Methoden, wie beispielsweise dem Freiburger Endophthalmitis-Set, ein Keimnachweis erfolgen. Bei der …

So erreichen Sie eine bestmögliche Wundheilung der Kornea

Die bestmögliche Wundheilung der Kornea, insbesondere ohne die Ausbildung von lichtstreuenden Narben, ist oberstes Gebot, um einer dauerhaften Schädigung der Hornhaut frühzeitig entgegenzuwirken und die Funktion des Auges zu erhalten.   

Update Augenheilkunde

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.