Abstract
Purpose: :
To further study the pathological mechanism of sulfur mustard (SM)– induced delayed keratopathy by comparing corneal innervation in impaired and non–impaired eyes, one month following exposure and correlate it with clinical parameters.
Methods: :
Animal Care and Use Committee approval at IIBR was obtained. Rabbit eyes were exposed to SM vapor and a clinical follow–up was carried out for one month, using slit–lamp biomicroscopy and pachymetry. At the end of the monitoring period, animals were euthanized, eyes enucleated and processed for histochemical evaluation. Eyes were divided into two groups of clinically impaired and non–impaired according to the appearance of neovascularization (NV) and/or bullae. The structure and density of nerves was studied in whole mount corneas, stained for cholinesterase activity. Quantitative analysis of neural density in central and peripheral corneal regions was carried out, by measurement of total nerve fiber length per defined area, using the Image–Pro software. Pearson correlation was performed between the clinical scores and neural density.
Results: :
Delayed injuries were observed in 50% of the SM–exposed corneas, representing two sub–populations of impaired and non–impaired. In general, SM exposed corneas were characterized by a large heterogeneity in neural density among different corneas and among different regions within the same cornea, in contrast to the homogeneous pattern of innervation observed in naïve corneas. Clinically impaired corneas displayed poor innervation and the total fiber length was significantly smaller compared to naïve (p<0.025) and non–impaired (p<0.009) corneas, in both peripheral and central regions. The non–impaired corneas contained even denser nerve network than naïve corneas, due to the extensive regenerative process. Significant correlations were found between neural density and corneal clinical score for both periphery (r=–0.75, p<0.01) and central (r=–0.55, p<0.05) corneal regions.
Conclusions: :
The reduced corneal innervation and the abnormal healing of corneal sensory nerves following SM exposure play a key role in the pathogenesis of long–term injuries that characterize 50% of the exposed eyes in our rabbit model. The prolonged damage of corneal nerves may stimulate chronic inflammation and may induce deficit of neurotrophic factors that are essential to maintain the integrity of normal corneal epithelium, thus indicate potential therapy.
Keywords: innervation: sensation • regeneration • neovascularization