Abstract
Corneal endothelial disease is a global sight-threatening disease, and corneal transplantation using donor corneas remains the sole therapeutic option. A previous work demonstrated that N (2)-alanyl-glutamine (Ala-Gln) protected against apoptosis and cellular stress, and maintained intestinal tissue integrity. In this pursuit, the present study aimed to examine the effect of Ala-Gln in the protection of the corneal endothelium and expand its range of potential clinical applications. Mice in the control group were intracamerally irrigated with Ringers lactate injection, whereas those in the experimental group were irrigated with Ringers lactate injection containing Ala-Gln. The mean intraocular pressure increased to 44 ± 3.5 mm Hg during intracameral irrigation (normal range 10.2 ± 0.4 mmHg). In vivo confocal microscopy results showed that the addition of Ala-Gln protected the morphology, structure, and density of the corneal endothelial cells. Optical Coherence Tomography (OCT) measurements showed that corneal thickness was not significantly different between the two groups, because of the immediate corneal edema after irrigation, but the addition of Ala-Gln obviously promoted the recovery of the corneal edema. Scanning electron microscopy indicated that the corneal endothelial cells were severely ruptured and exfoliated in the Ringer’s group accompanied with cellular edema, when compared with the Ala-Gln group. The intracameral irrigation using Ala-Gln protected the structure and expression of cytoskeleton and Na-K-ATPase, which exhibited a regular distribution and significantly increased expression in comparison to Ringer’s group. Furthermore, Ala-Gln maintained the mitochondrial morphology and increased the activity of mitochondria. Moreover, transmission electron microscopy showed that intracameral irrigation of Ala-Gln reversed the ultrastructural changes induced by the acute ocular hypertension in mice. Our study demonstrates that the intracameral irrigation of Ala-Gln effectively maintained the corneal endothelial pump function and barrier function by protecting the mitochondrial function and preventing the rearrangement of cytoskeleton in acute ocular hypertension in mice.
Highlights
The corneal endothelium located at the Descemet’s membrane, is a regular arrangement of hexagonal cells, which maintains the corneal transparency through stromal hydration, and acts as a barrier between the stroma and the anterior chamber (Riley et al, 1998; Bourne, 2003; Fischbarg and Maurice, 2004)
The intensity of the staining was analyzed, and a statistically significant decrease was observed in the Ringer’s corneal endothelium compared to the corneal endothelium irrigated with the addition of Ala-Gln at day 0, day 2 and day 10 (Figure 7H). These results indicate that the AlaGln group exhibited strong MitoTracker Red (MTR) staining, and the addition of AlaGln preserved the activity of mitochondria during the acute ocular hypertension due to intracameral irrigation in mice
The aim of this study was to detect the role of Ala-Gln in irrigation solutions, in an attempt to conclude whether it could protect the corneal endothelium
Summary
The corneal endothelium located at the Descemet’s membrane, is a regular arrangement of hexagonal cells, which maintains the corneal transparency through stromal hydration, and acts as a barrier between the stroma and the anterior chamber (Riley et al, 1998; Bourne, 2003; Fischbarg and Maurice, 2004). The corneal endothelium is responsible for pumping fluid out of the corneal stroma to prevent the development of edematous haze. An excessive decrease in the endothelial cell density can result from surgeries or accidental trauma, which can induce the damage of barrier and pump functions, and lead to an irreversible corneal edema, haze, and eventually loss of visual acuity (Joyce, 2003). The introduction of new transplantation techniques, such as Descemet’s membrane endothelial Keratoplasty, have decreased the risk of corneal transplantation techniques (Melles et al, 2008; Price and Price, 2010), there are still problems in the surgery, such as technical difficulties in surgery, graft rejection, cell loss, and donor corneal shortage. In order to protect the corneal endothelium effectively, there is an urgent need to investigate novel and sustainable treatments
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