Acute ocular hypertension disrupts barrier integrity and pump function in rat corneal endothelial cells

Abstract

Acute ocular hypertension (AOH) frequently compromises corneal endothelial cell (CEC) function in clinical practice. This type of stress induces corneal oedema and a decrease in the corneal endothelial cell density (ECD). The anterior chamber of the right eye of Sprague-Dawley rats was irrigated with Balanced Salt Solution (BSS) for two hours, and the left eye served as a control to determine the time-dependent effects of AOH on endothelial cell morphology and function. The average intraocular pressure (IOP) increased to 82.6 ± 2.3 mmHg (normal range: 10.2 ± 0.4 mmHg) during anterior irrigation. Very soon after initiating irrigation, corneal oedema became evident and the cornea exhibited a significant increase in permeability to FITC-dextran. The peripheral ECD was significantly reduced, and the morphology of CECs became irregular and multiform. The structures of the zonula occludens-1 (ZO-1) and F-actin were severely disrupted. In addtion, Na,K-ATPase exhibited a dispersed expression pattern. Two days after irrigation, obvious CEC proliferation was observed, the ECD recovered to a normal level, and F-actin was dispersed throughout the cytoplasm. Seven days later, the CEC structure and function were nearly normalized. Based on the results obtained using this model, an acute IOP crisis exerts transient deleterious effects on CEC structure and function in rats.

Characteristics of the Corneal Endothelium Across the Primary Angle Closure Disease Spectrum

“…Interestingly, a recent study on a rat model showed that an acute increase in IOP resulted in structural and functional damage of corneal endothelial cells, which gradually reversed when the acute rise in IOP resolved. 18 However, some studies [11][12][13][14][15] have shown significant decrease in ECD in eyes with a history of APAC. The variable interval between performing specular microscopy and an acute attack or duration of the acute attack across different studies, may contribute to the conflicting associations of APAC and ECD.…”

“…Endothelial cell loss has been reported in primary open angle glaucoma (POAG), 6,7 pigmentary, 8 pseudo exfoliation, 9 inflammatory glaucoma, 10 following an acute angle-closure attack [11][12][13][14][15] and primary angle closure glaucoma (PACG) 15,16 ; however, a few contradictory studies did not find such association of endothelial cell loss in glaucoma. 17,18 Many of the previous studies that reported lower endothelial cell density (ECD) in angle closure glaucoma have compared them with normal controls that had not undergone any laser procedures. In a comparative study, Varadaraj et al 19 compared the ECD in eyes with open angles and those with various stages of untreated angle closure disease.…”

Comprehensive treatment of patients with refractory glaucoma complicated by bullous keratopathy

“…Various authors have reported a relationship between elevated IOP and damage to the corneal endothelial cells as well as a negative correlation relationship between the density of the corneal endothelial cells and an acute IOP elevation [4,16,26].…”

Rate of central corneal thickness changes in primary angle closure eyes: long-term follow-up results

“…Varadaraj et al and Verma et al studied endothelial changes in the PAC disease spectrum, including eyes with a history of acute angle closure attack and found no significant difference in all groups [ 52 , 53 ]. Interestingly, a recent study of a rat model showed eyes with acute angle closure had lower ECD at first, but showed a gradual resolution once IOP stabilized to normal levels [ 54 ]. It may be more useful to assess endothelial changes since CCT does not reflect the overall corneal status.…”