April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
NON-HUMAN PRIMATE (NHP) OPTIC NERVE HEAD (ONH) PROTEOMIC CHANGE IN EARLY EXPERIMENTAL GLAUCOMA (EEG)
Author Affiliations & Notes
  • Claude Burgoyne
    Optic Nerve Head Research Laboratory, Devers Eye Institute, Portland, OR
  • Cheri Stowell
    Optic Nerve Head Research Laboratory, Devers Eye Institute, Portland, OR
  • Geeng-Fu Jang
    Cole Eye Institute, Cleveland Clinic, Cleveland, OH
    Lerner Research Institute, Cleveland Clinic, Cleveland, OH
  • Lei Zhang
    Cole Eye Institute, Cleveland Clinic, Cleveland, OH
    Lerner Research Institute, Cleveland Clinic, Cleveland, OH
  • Belinda Willard
    Lerner Research Institute, Cleveland Clinic, Cleveland, OH
  • Jack S Crabb
    Cole Eye Institute, Cleveland Clinic, Cleveland, OH
    Lerner Research Institute, Cleveland Clinic, Cleveland, OH
  • John W Crabb
    Cole Eye Institute, Cleveland Clinic, Cleveland, OH
    Lerner Research Institute, Cleveland Clinic, Cleveland, OH
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4555. doi:
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      Claude Burgoyne, Cheri Stowell, Geeng-Fu Jang, Lei Zhang, Belinda Willard, Jack S Crabb, John W Crabb; NON-HUMAN PRIMATE (NHP) OPTIC NERVE HEAD (ONH) PROTEOMIC CHANGE IN EARLY EXPERIMENTAL GLAUCOMA (EEG). Invest. Ophthalmol. Vis. Sci. 2014;55(13):4555.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To study the molecular mechanisms underlying ONH remodeling in NHP EEG1 and discover candidate blood-borne biomarkers, we quantified ONH proteomic change in Rhesus Macaques with laser-induced, unilateral EEG (0-30% optic nerve (ON) axon loss)2.

Methods: An ONH trephine (6mm) containing peripapillary sclera, retina and retrolaminar ON (≈2 mm behind the globe) was obtained from the EEG/control eyes of 4 adult NHP (3 high IOP (IOP Max >28 mm Hg), and 1 low IOP (IOP Max < 20 mm Hg)). Protein was extracted in SDS and digested with trypsin. Peptides were labeled with iTRAQ tags, fractionated by chromatography, and analyzed by LC MS/MS. Proteins were identified using the Swiss-Protein human database; iTRAQ tags were quantified by the weighted averaged method. Proteins were significantly altered when average ratios (EEG/ control) determined with ≥ 2 unique peptides in the 3 high (or 1 low) IOP animals were at least 1 standard deviation (SD) from the mean (p values ≤ 0.05). Bioinformatics analyses utilized Ingenuity Pathway Analysis.

Results: Among 1122 proteins identified in the high IOP animals, 55 were significantly increased and 68 were significantly decreased in the EEG ONH. Proteins significantly increased ≥ 2SD included chondroadherin, pigment epithelium-derived factor, biglycan, heterogenous nuclear ribonucleoprotein Q and R, and Fibulin-1. Proteins significantly decreased ≥ 2SD included alpha-tubulin N-acetyltransferase, hyaluronan and proteoglycan link protein 2, NAD-dependent protein deacetylase sirtuin-2, Dihydropteridine reductase, and 7 myelin associated proteins. Altered proteins or the direction of protein alteration were often different in the low IOP EEG ONH.

Conclusions: Top canonical pathways associated with altered ONH proteins in high IOP NHP EEG included actin cytoskeletal signaling, epithelial adherens junction signaling/remodeling and axon guidance signaling. Top networks included cellular assembly and organization. While additional animals must be studied, proteomic differences between low/high IOP EEG ONH may represent earlier/later stages of early ONH damage.3 Altered proteins provide insights into the molecular mechanisms underlying early ONH alterations in NHP EEG and suggest candidate blood-borne biomarkers for its systemic detection. 1Burgoyne. Exp Eye Res 2011 2He, et al. IOVS 2013. In Press. 3Howell, et al. J Clin Invest 2011

Keywords: 577 lamina cribrosa • 663 proteomics • 430 astrocytes: optic nerve head  
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