Prolonged Unilateral IOP Elevation in the Human Eye Results in Regionally Specific Glial Reactivity in the Retina and Lamina Cribrosa

Abstract

Purpose : We have established a model of unilateral elevation in intraocular pressure (IOP) in the human eye in research-consented brain-dead organ donors. This model can be used to investigate the initial cellular morphological and subcellular changes that occur regionally in the human retina and optic nerve head (ONH) as a result of the elevated IOP insult.

Methods : Research-consented brain-dead organ donors underwent an ocular examination with biometry, fundoscopy, optic nerve and retinal imaging with spectral domain optical coherence tomography and electroretinography (ERG). Prior to organ procurement, baseline IOP was measured, and IOP was elevated to 30 mmHg by injection of Viscoelastic into the anterior chamber (Healon PRO Ophthalmic, Johnson & Johnson, Inc). ERG (LKC Technologies), IOP, and blood pressure measurements were obtained every two hours until organ procurement (8-30 hours). Following organ procurement, eyes were enucleated and fixed in 10% formalin. The ONH, macula, and regional retinal sections were obtained for immunohistochemistry, and ONH and regional retinal sections were also obtained for RNA and protein analysis.

Results : Selective reductions in photopic negative response (PhNR) amplitudes and latencies indicate that an elevation in IOP specifically affects the inner retina of the human eye during our prolonged IOP protocol. Following elevated IOP, glial reactivity was elevated in the ONH. Astrocyte reactivity (GFAP) was greatest in the inferotemporal region of the LC, and microglial reactivity (Iba1) was greatest in the posterior LC compared with the untreated fellow eye. In the regional retinal sections, elevated IOP also resulted in an increase in microglial reactivity (Iba1) in the inner nuclear layer (INL) of the retina.

Conclusions : Acute prolonged elevation of IOP induced regionally specific elevated microglial and astrocytic reactivity in the LC of the ONH. The inferotemporal region of the LC, the region most susceptible to glaucomatous injury, exhibited elevated GFAP. Iba1 staining was greatest in the posterior LC. In the regional retinal sections, there was evidence of increased microglial reactivity and infiltration into the INL following prolonged elevated IOP. We continue to investigate other markers of inflammation and changes in cellular morphology and cell signaling in the retinas and ONHs of these treated and control eyes.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.