Increased Complement-Associated Inflammation in Cytomegalovirus-Positive Hypertensive Anterior Uveitis Patients Based on the Aqueous Humor Proteomics Analysis

Abstract

Herpetic anterior uveitis-associated ocular inflammation is commonly manifested with ocular hypertension and glaucoma. Relative to other viruses, cytomegalovirus (CMV) positive hypertensive anterior uveitis is associated with high recurrences of uveitis, as well as with uncontrolled intraocular pressure (IOP) and a subsequent higher requirement for future glaucoma surgery. To gain novel insights into the pathogenesis of ocular hypertension in these patients, we investigated the proteome changes of the aqueous humor (AH) derived from the CMV hypertensive anterior uveitis (CMV-HAU; n = 10) patients and non-glaucoma (cataract; n = 10) patients using liquid chromatography with tandem mass spectrometry. Among a total of 562 proteins identified, fifty and fifteen proteins were significantly elevated and decreased, respectively, in the AH of CMV-HAU patients compared to the control subjects by ≥2 fold. Gene ontology (GO) enrichment and network analyses of elevated proteins revealed that the enrichment of protein was involved in the complement activation, the humoral immune response mediated by the circulating immunoglobulins, proteolysis, and platelet degranulation. In the AH of CMV-HAU, GDF (growth/differentiation factor)-15, the inflammatory marker belonging to the TGF-β superfamily proteins, was significantly increased, while vasorin, an anti-TGF-β protein, levels were decreased. The trabecular meshwork cells infected with CMV exhibited a significantly increased expression of inflammatory markers. Collectively, these data indicate increased complement factor associated inflammation and humoral immunity in CMV-HAU associated ocular hypertension.

Analysis of risk factors associated with secondary open-angle glaucoma in Posner-Schlossman syndrome: A retrospective case-control study

“…Chee et al showed that up to 52.2% of patients with PSS were CMV-positive ( 21 ), which is generally consistent with our findings. Comparison of CMV-positive and CMV-negative PSS patients showed that the former had significant loss of corneal endothelial cells and the density was significantly lower than the latter, which may be associated with CMV attacking the trabecular meshwork endothelial cells and corneal endothelial cells, resulting in increased IOP and corneal endothelial cell loss ( 24 , 25 ). Su et al found that ganciclovir inhibits CMV viral activity and thus reduces the damage of trabecular meshwork endothelium and corneal endothelium ( 26 ), thereby decreasing the risk of advanced glaucoma.…”

AHP DB: a reference database of proteins in the human aqueous humor

“…Consequently, researchers have investigated changes within the AH proteome associated with different pathophysiological conditions ( 7 , 8 , 10–26 ). These investigations have led to evidence linking specific AH proteins to ocular diseases, such as cataracts ( 12 , 15 , 19 , 23 ), glaucoma ( 15 , 18 , 21 , 27 ), age-related macular degeneration ( 20 , 22 ), uveitis ( 28 , 29 ), retinoblastoma ( 30 , 31 ) and diabetic retinopathy ( 17 , 24 ). Moreover, the dynamics of the AH proteome have been observed to vary across demographic variables, such as sex ( 13 ) and race ( 32 ), with certain proteins involved in inflammatory protection and immune response found to be more abundant in AH samples from female and African American cohorts, respectively.…”