Early ultrastructural damage in retina and optic nerve following intraocular pressure elevation

Abstract

Elevated intraocular pressure (IOP) is a significant risk factor for glaucoma, causing structural and functional damage to the eye. Increased IOP compromises the metabolic and structural integrity of retinal ganglion cell (RGC) axons, leading to progressive degeneration and influencing the ocular immune response. This study investigated early cellular and molecular changes in the retina and optic nerve (ON) following ocular hypertension (OHT). A pigmented rat model was used, with OHT induced through low-temperature cauterization of the limbal vascular plexus. To assess the effects at early time points after OHT, transmission electron microscopy (TEM) was employed to analyze ultrastructural changes in the retina and ON, while immunofluorescence was used to evaluate cellular responses. Flow cytometry was used to examine alterations in immune-cell populations. Within 24 h post-OHT, ultrastructural changes were detected in the cytoplasm of RGCs, indicating early cellular alterations undetectable by conventional microscopy. These ultrastructural modifications progressed further at 48 and 72 h, despite the absence of overt RGC loss or disruptions in retinal layer integrity. Changes in the axons and nodes of Ranvier were evident within the first 24 h after ocular hypertension, becoming more pronounced by 72 h. These findings offer novel insights into the early pathogenesis of glaucoma, highlighting critical early impacts that could guide the development of new therapeutic strategies to prevent irreversible RGC loss.