Abstract
Purpose :
Elevated intraocular pressure is a primary risk factor for glaucomatous optic neuropathy. The acute
immune response to elevation in IOP in animal models has been described, however, the exact molecular
pathways that trigger these response remains unknown in the human eye. This study evaluates the impact of
acute elevation in IOP in the living human eye on transcriptional genes responsible for immune recruitment
seen with early injury in the retina.
Methods :
Research-consented brain-dead organ donors underwent screening for inclusion criteria. Blood
pressure was monitored via an arterial line and tonometry was performed using an applanation tonometer.
The experimental eye received one hour of manometric pressure elevation at 50 mmHg via pars plana
cannulation while the fellow eye served as a control. Electroretinography was performed in regular intervals.
Ocular tissues were subsequently procured, dissected, formalin-fixed and paraffin embedded. Retina was
sliced in 5 µm sections, deparaffinized and RNA fluorescent in-situ hybridization was performed according to
RNAscope (Advanced Cell Diagnostics) protocol for FFPE tissues.
Results :
Acute, 1-hour, sub-ischemic, increase in IOP results in an increase in transcripts involved in innate
immune activation as well as recruitment of peripheral immune effector cells. To date, we analyzed one
donor, and found an increase in chemokine ligand 2 (CCL2), FasR, cluster of differentiation 44 (CD44),
transforming growth factor beta 1 (TGF-β1). Analysis is ongoing.
Conclusions :
Brief, acute increases in IOP results in alteration in the transcription of genes involved in early
immune and senescent pathways in the living human retina. Further studies of this acute response within the
living human eye could further elucidate early injurious pathways at the onset of ocular hypertension.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.