September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Initial Changes in Optic Nerve Head (ONH) MicroRNA (miR) Expression Following a Controlled Elevation of Intraocular Pressure (IOP)
Author Affiliations & Notes
  • Hari Jayaram
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • William O Cepurna
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Tiffany Choe
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Diana Lozano
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Dongseok Choi
    Public Health & Preventive Medicine, Oregon Health & Science University, Portland, Oregon, United States
  • Shandiz Tehrani
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Elaine C Johnson
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • John C Morrison
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   Hari Jayaram, Allergan (R); William Cepurna, None; Tiffany Choe, None; Diana Lozano, None; Dongseok Choi, None; Shandiz Tehrani, None; Elaine Johnson, None; John Morrison, None
  • Footnotes
    Support  The US-UK Fulbright Commission in conjunction with Fight for Sight and The Special Trustees of Moorfields Eye Hospital (HJ). The National Institutes of Health Grants: R01EY010145 (JCM), P30 EY010572 (OHSU Core Grant) and an unrestricted grant from Research to Prevent Blindness (RPB), Inc. JCM is a RPB Senior Investigator.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2526. doi:
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      Hari Jayaram, William O Cepurna, Tiffany Choe, Diana Lozano, Dongseok Choi, Shandiz Tehrani, Elaine C Johnson, John C Morrison; Initial Changes in Optic Nerve Head (ONH) MicroRNA (miR) Expression Following a Controlled Elevation of Intraocular Pressure (IOP). Invest. Ophthalmol. Vis. Sci. 2016;57(12):2526.

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

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Abstract

Purpose : MiRs are small, endogenous non-coding RNAs that modulate post-transcriptional gene expression. As early optic nerve damage from elevated IOP is known to produce significant gene expression changes within the ONH, we hypothesized that a controlled elevation of IOP (CEI) sufficient to cause axon damage would induce altered miR expression within the ONH.

Methods : Unilateral anterior chamber cannulation was performed in anesthetized rats, raising IOP to 60 mmHg for 8 hours. Temperature, oxygen saturation and blood pressure were monitored throughout. Immediate sacrifice was performed following the CEI exposure. Total RNA was extracted from ONHs of the experimental eyes(n=4) and from naïve rats as controls(n=4). Optic nerves from an additional group of 16 animals were studied at 10 days post-CEI to look for axon damage. RNA was reverse transcribed, pre-amplified and evaluated on miR PCR Array Cards able to detect 754 mature miRs. Differentially expressed miRs were identified by the ΔΔCt method following global normalization. Statistical comparison was performed using a two-tailed t-test with significance considered for values of p<0.05, stratified for fold changes larger than ±2. A systematic review of published literature for each individual miR was used to derive potential functional interpretations.

Results : Evaluation of optic nerves from the additional rats showed small focal areas of axon degeneration at 10 days post-CEI. The arrays detected 435 miRs,19 significantly down and 11 up regulated in ONHs exposed to a CEI, compared to controls (see figure & table). Down regulated miRs were associated with enhanced cell proliferation, inflammatory responses, TGFβ signaling and apoptosis, reduced angiogenesis and actin cytoskeleton disruption. Up regulated miRs appeared more protective, providing feedback to limit the effects of inflammation, apoptosis and TGFβ signaling, and also to promote axon plasticity and Schwann cell proliferation.

Conclusions : Altered miR expression is evident within the ONH immediately post-CEI. The biological sequelae of down regulated miRs are often counterbalanced by the upregulated miRs, which also act to promote axon survival. Further studies investigating the dynamic nature of miR responses within the ONH following a single CEI exposure will further advance our understanding of the complex pathophysiology of glaucomatous optic neuropathy.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

 

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