July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Dynamic Changes in Optic Nerve Head (ONH) MicroRNA (miR) Expression Following a Controlled Elevation of Intraocular Pressure (IOP)
Author Affiliations & Notes
  • Hari Jayaram
    Glaucoma Service, NIHR Moorfields Biomedical Research Centre, UK, London, United Kingdom
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Diana C Lozano
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Tiffany Choe
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • William Cepurna
    Casey Eye Institute, 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); Diana Lozano, None; Tiffany Choe, None; William Cepurna, None; Shandiz Tehrani, None; Elaine Johnson, None; John Morrison, None
  • Footnotes
    Support  NIH-RO1EY010145 (JCM), NIH-RO1EY010145-S1 (DCL), NIH-T32EY023211 (DCL), NIH-K08EY024025 (ST), RPB Career Development Award (ST), The US-UK Fulbright Commission in conjunction with Fight for Sight and The Special Trustees of Moorfields Eye Hospital (HJ), NIH-P30EY01572 (OHSU), and an unrestricted grant from Research to Prevent Blindness (OHSU).
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3738. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Hari Jayaram, Diana C Lozano, Tiffany Choe, William Cepurna, Shandiz Tehrani, Elaine C. Johnson, John C Morrison; Dynamic Changes in Optic Nerve Head (ONH) MicroRNA (miR) Expression Following a Controlled Elevation of Intraocular Pressure (IOP). Invest. Ophthalmol. Vis. Sci. 2018;59(9):3738.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : MiRs are small, endogenous non-coding RNAs that negatively regulate post-transcriptional gene expression. We have previously shown that controlled elevation of IOP (CEI) for 8 hours causes significant changes in miR expression within the ONH. This study aimed to describe the dynamic pattern of changing miR expression within the ONH during the first ten days following CEI.

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. Total RNA was extracted from ONHs of the experimental eyes immediately after CEI exposure and at 12hrs, 1,2, 3, 7 & 10 days, with ONHs from naïve rats as controls (n=8/group). 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 2-tailed t-test with significance considered for values of p<0.05, stratified for fold changes larger than ±2. Curated online databases were used to identify the likely pathways influenced by individual miRs.

Results : MiR downregulation dominated immediate responses (↑gene expression/biological activity). This gradually reversed, with miR upregulation (↓gene expression/biological activity) more prevalent in the days after CEI (see Figure). Early (day 1) and late (days 7&10) downregulation of miRs 1191&200b was seen, serving to enhance axon guidance and cell proliferation. This counterbalanced the dominant effect of miR upregulation at days 7&10 (miRs-1193, 302a, 449 & 130b), predicted to reduce axon guidance and neurotrophin signaling. Upregulation of miRs 449,302a and 1193 was seen from day 1 onwards, predicted to attenuate apoptotic pathways. Downregulation of miR-184 was observed between days 1-10, which would be expected to increase signal transduction, synaptic transmission and neuron projection development.

Conclusions : Dynamic changes in miR expression occur within the ONH in the days following CEI. The biological sequelae of downregulated miRs are often counterbalanced by the upregulated miRs, many of which may act to promote axon survival. Integration of ONH microRNA and gene expression will enhance our understanding of the complex biological responses to IOP elevation.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×