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Primed Mycobacterial Uveitis PMU as a Model for Post-Infectious Uveitis
Published on: December 17, 2021
Increased Complement-Associated Inflammation in Cytomegalovirus-Positive Hypertensive Anterior Uveitis Patients Based
Jin A Choi1, Hyun-Hee Ju1, Jiyoung Lee2
1Department of Ophthalmology, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon 16247, Korea.
Insights
Cytomegalovirus (CMV) positive hypertensive anterior uveitis involves increased inflammation and immune responses in the eye's aqueous humor. This suggests a link between CMV infection and elevated intraocular pressure, potentially leading to glaucoma.
Area of Science:
- Ophthalmology
- Immunology
- Proteomics
Background:
- Herpetic anterior uveitis frequently causes ocular hypertension and glaucoma.
- Cytomegalovirus (CMV) positive hypertensive anterior uveitis shows high recurrence rates and uncontrolled intraocular pressure (IOP), increasing the need for glaucoma surgery.
Purpose of the Study:
- To investigate proteomic changes in aqueous humor (AH) of patients with CMV-positive hypertensive anterior uveitis (CMV-HAU).
- To understand the pathogenesis of ocular hypertension in CMV-HAU patients.
Main Methods:
- Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to analyze aqueous humor proteomes.
- Comparison between CMV-HAU patients (n=10) and control cataract patients (n=10).
- Gene ontology (GO) enrichment and network analyses were performed on identified proteins.
Main Results:
- A total of 562 proteins were identified in the aqueous humor.
- Fifty proteins were significantly elevated and fifteen were decreased (≥2 fold) in CMV-HAU patients compared to controls.
- Elevated proteins were enriched in pathways including complement activation, humoral immune response, proteolysis, and platelet degranulation.
- Increased levels of inflammatory marker GDF-15 and decreased levels of anti-TGF-β protein vasorin were observed in CMV-HAU patients.
- CMV-infected trabecular meshwork cells showed increased inflammatory marker expression.
Conclusions:
- CMV-HAU associated ocular hypertension is characterized by increased complement factor-associated inflammation.
- Humoral immunity plays a significant role in the pathogenesis of CMV-HAU.
- These findings provide insights into the molecular mechanisms underlying ocular hypertension in CMV-HAU.
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.
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