Molecular similarities and differences between human and rat retinas in glaucoma

Research output: Contribution to journalMeeting abstractResearchpeer-review

Abstract

Purpose : Glaucoma is a progressive neurodegenerative disease of the eye characterised by progressive loss of retinal ganglion cells (RGCs) in the inner retina. The molecular mechanism(s) that result in RGC dysfunction in various optic neuropathies, however, remain ill-defined. This study was aimed to investigate the molecular basis of glaucoma pathogenesis by taking a systems-level perspective of the human retinal proteome and compare it with experimental glaucoma animal model using unbiased quantitative proteomics approaches. Methods : Multiplexed Tandem Mass Tag based proteomics (TMT-MS3) was carried out on retinal and vitreous humour collected from glaucoma patients and age-matched controls (average ages: control 64.5 ± 10, n = 10 and glaucoma: 71.5 ± 8.5, n = 10, respectively). A rat model of glaucoma was generated using weekly microbead injections into the anterior chamber of the eye to help increase the intraocular pressure (n: 10). The differentially expressed proteins identified based on a two-sample t-test (p < 0.05) and a fold change threshold (≥1.3 for up-regulation or ≤0.76 for down-regulation). Finally, selected markers were validated using western blotting and electrochemiluminescence assay. Results : About 5000 proteins were quantified from both the human and experimental glaucoma model. Pathway analyses of differentially regulated proteins indicated specific activation of classical complement pathway (up-regulation of C1q, C1s, C1r, C4a, C4b, C3, C5, C6, C7, C8a, C8b, C8g and C9 proteins) and cholesterol metabolism (up-regulation of APOA1, APOA4, APOC1, APOC3, APOH, APOB, APOE, APOL1, APOM, APOA2, APOL2 and APOC2 proteins) in human glaucoma retinas specifically suggesting an innate inflammatory response. Molecular dysregulation of oxidative phosphorylation (down-regulation of electron transport chain complex proteins), protein folding (down-regulation of crystalline proteins) and glutathione biosynthesis pathways (up-regulation of GSTs), were identified in both human and animal glaucoma model.
LanguageEnglish
Pages3531
Number of pages1
JournalIOVS
Volume59
Issue number9
Publication statusPublished - 2018
EventAnnual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) 2018 - Honolulu, United States
Duration: 29 Apr 20183 May 2018

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Glaucoma
Retina
Up-Regulation
Down-Regulation
Retinal Ganglion Cells
Proteins
Electron Transport Chain Complex Proteins
Proteomics
Animal Models
Classical Complement Pathway
Vitreous Body
Optic Nerve Diseases
Oxidative Phosphorylation
Protein Folding
Apolipoproteins B
Protein Biosynthesis
Anterior Chamber
Apolipoproteins E
Proteome
Intraocular Pressure

Cite this

@article{81e2f2e459da4c41a7a2d6abc870ba7d,
title = "Molecular similarities and differences between human and rat retinas in glaucoma",
abstract = "Purpose : Glaucoma is a progressive neurodegenerative disease of the eye characterised by progressive loss of retinal ganglion cells (RGCs) in the inner retina. The molecular mechanism(s) that result in RGC dysfunction in various optic neuropathies, however, remain ill-defined. This study was aimed to investigate the molecular basis of glaucoma pathogenesis by taking a systems-level perspective of the human retinal proteome and compare it with experimental glaucoma animal model using unbiased quantitative proteomics approaches. Methods : Multiplexed Tandem Mass Tag based proteomics (TMT-MS3) was carried out on retinal and vitreous humour collected from glaucoma patients and age-matched controls (average ages: control 64.5 ± 10, n = 10 and glaucoma: 71.5 ± 8.5, n = 10, respectively). A rat model of glaucoma was generated using weekly microbead injections into the anterior chamber of the eye to help increase the intraocular pressure (n: 10). The differentially expressed proteins identified based on a two-sample t-test (p < 0.05) and a fold change threshold (≥1.3 for up-regulation or ≤0.76 for down-regulation). Finally, selected markers were validated using western blotting and electrochemiluminescence assay. Results : About 5000 proteins were quantified from both the human and experimental glaucoma model. Pathway analyses of differentially regulated proteins indicated specific activation of classical complement pathway (up-regulation of C1q, C1s, C1r, C4a, C4b, C3, C5, C6, C7, C8a, C8b, C8g and C9 proteins) and cholesterol metabolism (up-regulation of APOA1, APOA4, APOC1, APOC3, APOH, APOB, APOE, APOL1, APOM, APOA2, APOL2 and APOC2 proteins) in human glaucoma retinas specifically suggesting an innate inflammatory response. Molecular dysregulation of oxidative phosphorylation (down-regulation of electron transport chain complex proteins), protein folding (down-regulation of crystalline proteins) and glutathione biosynthesis pathways (up-regulation of GSTs), were identified in both human and animal glaucoma model.",
author = "Mehdi Mirzaei and Vivek Gupta and Nitin Chitranshi and Yunqi Wu and Graham, {Stuart L.}",
year = "2018",
language = "English",
volume = "59",
pages = "3531",
journal = "IOVS",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology",
number = "9",

}

Molecular similarities and differences between human and rat retinas in glaucoma. / Mirzaei, Mehdi; Gupta, Vivek; Chitranshi, Nitin; Wu, Yunqi; Graham, Stuart L.

In: IOVS, Vol. 59, No. 9, 2018, p. 3531.

Research output: Contribution to journalMeeting abstractResearchpeer-review

TY - JOUR

T1 - Molecular similarities and differences between human and rat retinas in glaucoma

AU - Mirzaei, Mehdi

AU - Gupta, Vivek

AU - Chitranshi, Nitin

AU - Wu, Yunqi

AU - Graham, Stuart L.

PY - 2018

Y1 - 2018

N2 - Purpose : Glaucoma is a progressive neurodegenerative disease of the eye characterised by progressive loss of retinal ganglion cells (RGCs) in the inner retina. The molecular mechanism(s) that result in RGC dysfunction in various optic neuropathies, however, remain ill-defined. This study was aimed to investigate the molecular basis of glaucoma pathogenesis by taking a systems-level perspective of the human retinal proteome and compare it with experimental glaucoma animal model using unbiased quantitative proteomics approaches. Methods : Multiplexed Tandem Mass Tag based proteomics (TMT-MS3) was carried out on retinal and vitreous humour collected from glaucoma patients and age-matched controls (average ages: control 64.5 ± 10, n = 10 and glaucoma: 71.5 ± 8.5, n = 10, respectively). A rat model of glaucoma was generated using weekly microbead injections into the anterior chamber of the eye to help increase the intraocular pressure (n: 10). The differentially expressed proteins identified based on a two-sample t-test (p < 0.05) and a fold change threshold (≥1.3 for up-regulation or ≤0.76 for down-regulation). Finally, selected markers were validated using western blotting and electrochemiluminescence assay. Results : About 5000 proteins were quantified from both the human and experimental glaucoma model. Pathway analyses of differentially regulated proteins indicated specific activation of classical complement pathway (up-regulation of C1q, C1s, C1r, C4a, C4b, C3, C5, C6, C7, C8a, C8b, C8g and C9 proteins) and cholesterol metabolism (up-regulation of APOA1, APOA4, APOC1, APOC3, APOH, APOB, APOE, APOL1, APOM, APOA2, APOL2 and APOC2 proteins) in human glaucoma retinas specifically suggesting an innate inflammatory response. Molecular dysregulation of oxidative phosphorylation (down-regulation of electron transport chain complex proteins), protein folding (down-regulation of crystalline proteins) and glutathione biosynthesis pathways (up-regulation of GSTs), were identified in both human and animal glaucoma model.

AB - Purpose : Glaucoma is a progressive neurodegenerative disease of the eye characterised by progressive loss of retinal ganglion cells (RGCs) in the inner retina. The molecular mechanism(s) that result in RGC dysfunction in various optic neuropathies, however, remain ill-defined. This study was aimed to investigate the molecular basis of glaucoma pathogenesis by taking a systems-level perspective of the human retinal proteome and compare it with experimental glaucoma animal model using unbiased quantitative proteomics approaches. Methods : Multiplexed Tandem Mass Tag based proteomics (TMT-MS3) was carried out on retinal and vitreous humour collected from glaucoma patients and age-matched controls (average ages: control 64.5 ± 10, n = 10 and glaucoma: 71.5 ± 8.5, n = 10, respectively). A rat model of glaucoma was generated using weekly microbead injections into the anterior chamber of the eye to help increase the intraocular pressure (n: 10). The differentially expressed proteins identified based on a two-sample t-test (p < 0.05) and a fold change threshold (≥1.3 for up-regulation or ≤0.76 for down-regulation). Finally, selected markers were validated using western blotting and electrochemiluminescence assay. Results : About 5000 proteins were quantified from both the human and experimental glaucoma model. Pathway analyses of differentially regulated proteins indicated specific activation of classical complement pathway (up-regulation of C1q, C1s, C1r, C4a, C4b, C3, C5, C6, C7, C8a, C8b, C8g and C9 proteins) and cholesterol metabolism (up-regulation of APOA1, APOA4, APOC1, APOC3, APOH, APOB, APOE, APOL1, APOM, APOA2, APOL2 and APOC2 proteins) in human glaucoma retinas specifically suggesting an innate inflammatory response. Molecular dysregulation of oxidative phosphorylation (down-regulation of electron transport chain complex proteins), protein folding (down-regulation of crystalline proteins) and glutathione biosynthesis pathways (up-regulation of GSTs), were identified in both human and animal glaucoma model.

M3 - Meeting abstract

VL - 59

SP - 3531

JO - IOVS

T2 - IOVS

JF - IOVS

SN - 0146-0404

IS - 9

ER -