Optic Nerve Head Gene Transcription Sequelae to a Single Elevated IOP Exposure Provides Insights into Known Responses to Chronically Elevated IOP

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 chronically elevated IOP glaucoma models. 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 mmHg. ONH RNA was harvested at 0 hr, and 1, 2, 3, 7, and 10 days after PT-CEI and normotensive-CEI, in addition to naive animals. RNA-Seq was performed to analyze ONH gene expression. The number of significantly changed genes peaked immediately (n of 1354) after the PT-CEI (0 hr). This was followed by a lull (less than 4 genes per time point) at 1 and 2 days post PT-CEI. Gene activity increased again at 3 days (136 genes) and persisted at 7 (78 genes) and 10 (339 genes) days. 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.