The authors thank Kate Keller for intellectual discussions and Tiffany E. Choe and Aryana Abtin for technical support with this project. Short read sequencing assays were performed by the OHSU Massively Parallel Sequencing Shared Resource, and RNA-seq analysis was performed by the Oregon National Primate Research Center Bioinformatics & Biostatistics Core, which is funded in part by NIH grant OD P51 OD011092. Supported by R01EY010145-17S1 (DCL), R01EY010145 (JCM), R01EY016866 (ECJ), R01EY030429 (ST), P51 OD011092 (OHSU National Primate Research Center), P30 EY010572 (Casey Eye Institute), and an unrestricted departmental grant to the Casey Eye Institute from Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science
Optic Nerves -- Gene expression responses
Purpose: To clarify the optic nerve head (ONH) gene expression responses associated with a single, axon-damaging exposure to elevated IOP in relation to the composite cellular events previously identified in models of chronically elevated IOP.
Methods: Anesthetized rats were exposed unilaterally to an 8-hour pulse-train controlled elevation of IOP (PT-CEI) at 60 mm Hg, while others received normotensive CEI at 20 mm Hg. ONH RNA was harvested at 0 hours and 1, 2, 3, 7, and 10 days after either CEI and from naïve animals. RNA sequencing was performed to analyze ONH gene expression. DAVID Bioinformatics tools were used to identify significant functional annotation clusters. Gene function was compared between PT-CEI and two models of chronic ocular hypertension from the literature.
Results: The number of significantly changed genes peaked immediately (n = 1354) after PT-CEI (0 hours). This was followed by a lull (point) at 1 and 2 days after PT-CEI. Gene activity increased again at 3 days (136 genes) and persisted at 7 (78 genes) and 10 (339 genes) days. Significant gene functional categories included an immediate upregulation of Defense Response at 0 hours, followed by upregulation in Cell Cycle, a reduction in Axonal-related genes at 3 to 10 days, and upregulation of Immune Response–related genes at 10 days following PT-CEI. The most commonly upregulated gene expression across our PT-CEI study and two chronic models of ocular hypertension were cell cycle related.
Conclusions: The PT-CEI model places in sequence ONH gene expression responses previously reported in models with chronically elevated IOP and may provide insights into their role in optic nerve damage.
Copyright 2023 The Authors This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Locate the Document
Lozano, D. C., Jayaram, H., Cepurna, W. O., Tehrani, S., Gao, L., Fei, S. S., ... & Morrison, J. C. (2023). Optic Nerve Head Gene Transcription Sequelae to a Single Elevated IOP Exposure Provides Insights Into Known Responses to Chronically Elevated IOP. Investigative Ophthalmology & Visual Science, 64(10), 4-4.