Insights into mustard gas keratopathy: Characterizing corneal layer-specific changes in mice exposed to nitrogen mustard.

Exposure to mustard agents, such as sulfur mustard (SM) and nitrogen mustard (NM), often results in ocular surface damage. This can lead to the emergence of various corneal disorders that are collectively referred to as mustard gas keratopathy (MGK). In this study, we aimed to develop a mouse model of MGK by using ocular NM exposure, and describe the subsequent structural changes analyzed across the different layers of the cornea. A 3 µL solution of 0.25 mg/mL NM was applied to the center of the cornea via a 2-mm filter paper for 5 min. Mice were evaluated prior to and after exposure on days 1 and 3, and weekly for 4 weeks using slit lamp examination with fluorescein staining. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) tracked changes in the epithelium, stroma, and endothelium of the cornea. Histologic evaluation and immunostaining were used to examine corneal cross-sections collected at the completion of follow-up. A biphasic ocular injury was observed in mice exposed to NM, most prominent in the corneal epithelium and anterior stroma. Following exposure, mice experienced central corneal epithelial erosions and thinning, accompanied by a decreased number of nerve branches in the subbasal plexus and increased activated keratocytes in the stroma. The epithelium was recovered by day 3, followed by exacerbated punctuate erosions alongside persistent stromal edema that arose and continued onward to four weeks post-exposure. The endothelial cell density was reduced on the first day after NM exposure, which persisted until the end of follow-up, along with increased polymegethism and pleomorphism. Microstructural changes in the central cornea at this time included dysmorphic basal epithelial cells, and in the limbal cornea included decreased cellular layers and p63+ area, along with increased DNA oxidization. We present a mouse model of MGK using NM that successfully replicates ocular injury caused by SM in humans who have been exposed to mustard gas. Our research suggests DNA oxidation contributes to the long-term effects of nitrogen mustard on limbal stem cells.

Association between apolipoprotein E polymorphism and nephropathy in Iranian diabetic patients.

Approximately one-third of diabetic patients develop evidence of nephropathy. Pathogenesis of diabetic nephropathy (DN) remains unclear; however, some genetic and metabolic risk factors have been determined for the development and progression of DN. In the recent genetic studies, polymorphism of apolipoprotein E (ApoE) gene has been reported as a risk factor for the development of DN; however, the results are inconsistent. The aim of the present study was to evaluate the association between ApoE polymorphism and nephropathy in Iranian patient with type 2 diabetes. A total of 197 patients with type 2 diabetes in two groups with and without nephropathy (n = 99 and n = 98, respectively) participated in this case-control study. ApoE genotype was determined by restriction fragment length polymorphism analysis. Biochemical factors of all patients were measured. The frequency of Apo ε4 allele was significantly (P <0.05) lower in DN patients (10.6%) than in diabetic patients without nephropathy (20.4%). No significant difference was observed between the groups regarding Apo ε2 and Apo ε3 allele frequencies. Serum level of total and low-density lipoprotein cholesterol in Apo ε2 carriers was lower than Apo ε3 and Apo ε4 carriers, but this difference was not statistically significant. Frequency of Apo ε4 allele is higher in diabetic patients without nephropathy than DN participants. Given to the result, it seems that Apo ε4 has a protective effect in diabetic patients against nephropathy.