In the current study, we also showed, to the best of our knowledge for the first time in the literature, an association between PON1 activity and the degree of corneal endothelium alterations in COPD patients. A decrease in serum PON1 activity has previously been reported in patients with diabetic retinopathy
32–34 and in patients with macular degeneration.
35,36 Hashim et al.
37,38 observed a decreased paroxonase activity in the serum of diabetic patients and senile individuals suffering from cataracts, and protein and mRNA PON1 expression in human cataractous lens tissue. Liton et al.
39 reported that the gene expression of PON3 (another antioxidant enzyme, genetically related to PON1) was down-regulated in POAG trabecular meshwork cells. The present study reports direct significant associations between serum PON1 activities and ECD, as well as inverse associations with corneal thickness in patients with cataracts, with or without COPD. Cataracts are a multifactorial disorder in which normal vision is impaired owing to the loss of lens transparency. One of the mechanisms that leads to the development of lens opacity is oxidative insult generated as a result of an imbalance between antioxidants and reactive oxygen species.
37 Earlier studies observed associations between antioxidant enzymes such as catalase, superoxide dismutase, and glutathione in cataracts.
40,41 Our study suggests that PON1 also plays a role in the protection of corneal endothelial cells from free radical–induced oxidative damage. In the present study, we were unable to determine PON1 (activity or concentration) in aqueous humor. This is not surprising since PON1 is carried in the circulation bound to HDL particles, and this lipoprotein is present in this fluid at very low concentrations.
42 The question arising is how peripheral PON1 can be associated with corneal endothelium alterations. The most likely explanation is that low serum PON1 activities do not efficiently protect from oxidative stress, and free radical species cross the blood–cornea barrier and, thus, affecting endothelial cells.
43 Free radicals can cause alterations in corneal endothelial cells via oxidation of cytoskeleton proteins, mainly vimentin and F-actin.
44,45 Along with oxidative stress, inflammation is one of the main pathophysiologic findings in COPD.
46,47 Indeed, oxidative stress and inflammation are interdependent phenomena, and exacerbate each other's effect.
25,48 In our study, we analyzed plasma TNFα concentrations as a marker of inflammation. This cytokine has been associated, in earlier studies, with other eye diseases such as glaucoma and cornea transplant rejection.
49,50 Evidence suggests that, similarly to oxidative stress, TNFα alters the actin filaments of the endothelial cell cytoskeleton.
51 Taken together, these changes in the cytoskeleton structure and function may cause morphologic and functional changes in the endothelial cells, and would ultimately produce cell death by apoptosis and a decrease in ECD.
52