Inflammation is a key factor in multiple diseases. It has been demonstrated that inflammation plays significant roles in the pathological processes of AMD, diabetic retinopathy and other ophthalmic diseases[17, 18]. Howel et al. found that in the early stage of glaucoma, microglial cells, glial cells, and immune cells from other blood sources can trigger a neuroinflammatory response. Other relevant studies have also suggested that pathological changes occur in synapses, dendrites and somatic cells in the early stage of glaucoma. The investigators in the previous studies have suggested that these changes probably result from a retinal inflammatory response in the early stage of glaucoma. The role of inflammation in the neurodegeneration caused by glaucoma is a popular research topic, but unclear yet.
In this study, we found that the pChE level in the APAC group (7450.89 ± 1748.49 IU/L) was significantly lower than that in the normal group (7994.68 ± 1321.90 IU/L). In addition, the pChE level in the APAC group was significantly lower than that in the CPACG group (7969.44 ± 1572.14 IU/L), whose IOP was much lower than that of the APAC group. There was a significant difference in pChE level between the APAC and CPACG groups (P < 0.001). There was no significant difference in sex among the three groups (P = 0.932). The average ages of the patients in the APAC, CPACG groups and normal subjects were 68.51 ± 5.42 years, 69.14 ± 5.91 years, 71.62 ± 5.84 years, respectively, with no significant difference among the three groups (P = 0.720). The previous results showed that BChE activity was negatively correlated with age, while it was positively correlated with triglyceride, cholesterol, and albumin concentrations[20, 21]. Therefore, in addition to other systemic factors that may cause changes in pChE, such as age, sex, and systemic diseases, we speculate that the acute inflammation of due to the rapid rise of IOP may be one of the main reasons for the significant difference in pChE. Narendra et al. also found that AChE level was lower in glaucoma subjects than in normal individuals. However, the number of 15 glaucoma patients selected in the previous study was limited, and individual differences were obvious. In addition, a study observing changes in AChE and pChE levels in 19 glaucoma patients with chronic glaucoma (without clear delineation of the type of glaucoma) within hours to two weeks revealed that the AChE level in the glaucoma group was lower than that in the normal control group.
In this study, we found that pChE level decreased when IOP increased in acute angle closure patients, consistent with results of Lampón et al. Lampón found a significant negative correlation between BChE and high-sensitivity C-reactive protein (hs-CRP). When the hs-CRP concentration was higher than 3 mg/L, there was a significant negative correlation between hs-CRP and BChE (P < 0.001). When patients had systemic acute inflammation (hs-CRP > 10 mg/L), the relationship between the two variables also supported this conclusion. C-reactive protein (CRP) is a ring-shaped pentameric protein synthesized by the liver. During inflammatory reactions, CRP is secreted into the blood after secretion of interleukin-6 by T-cells and macrophages. Various previous studies have shown that CRP is a biomarker of systemic inflammation. The findings indicate that a higher CRP level is associated with greater systemic inflammatory activity and lower BChE activity. In addition, studies have shown that the activity of BChE and other esterases is decreased in frail elderly individuals and that the decreased activity is associated with increased levels of inflammatory markers, suggesting that inflammation may mediate the effects of frailty on metabolism. All these results are similar to the acute inflammation caused by the acute increased IOP associated with glaucoma in this study.
Our results showed that in APAC patients, pChE was negatively correlated with IOP (r = -0.410, P < 0.001). However, there was no correlation in CPACG patients (P = 0.228). Some researchers have linked chronic low-grade inflammation (defined by CRP levels[25, 26] and BChE activity[27–29]) to metabolic syndrome, insulin resistance, obesity, and cardiovascular risk. I-te Lee et al suggested that the level of systemic inflammation can be reflected by the level of serum CRP and is related to high IOP in patients with and without metabolic syndrome. Although the pathological mechanism of the association of systemic inflammation and IOP is not clear, the results of their research showed a positive correlation between IOP and CRP levels. Higher systemic inflammatory activity is associated with lower BChE activity. Therefore, in this study, pChE decreased with increasing IOP. The negative correlation between BChE activity and inflammatory markers may be causal. Previous studies have revealed relationships between lower BChE activity and higher risks of mortality by acute stroke, cardiovascular disease and long-term dialysis, which may be caused by the negative correlation between BChE activity and inflammation grade. The significance of pChE and inflammation in glaucoma needs to be further explored.
There are several limitations of our present study. First, as it was a retrospective study, it focused on the changes in ChE levels in plasma. In the future, pChE and other inflammatory indexes could be further analyzed in the aqueous humor, and CRP could be detected in plasma. This will help to identify patients in different stages of glaucoma. In addition, investigation of the relationships between different levels of CRP and indexes such as pChE should be performed. Further studies to investigate the correlation between systemic inflammation and glaucoma are warranted.