Complement Activation in the Vitreous of Patients With Proliferative Diabetic Retinopathy

A growing body of evidence points to complement dysregulation in diabetes. Early studies have indicated the presence of complement components inside the eye in patients with diabetic retinopathy, but these data have been confounded by leakage of proteins from the systemic circulation into the vitreo...

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Published in:Investigative ophthalmology & visual science 2020-09, Vol.61 (11), p.39
Main Authors: Mandava, Nikhil, Tirado-Gonzalez, Vanessa, Geiger, Matthew D, Patnaik, Jennifer L, Frazer-Abel, Ashley, Lynch, Anne M, Mandava, Naresh, Palestine, Alan G, Holers, V Michael, Wagner, Brandie D, Sanchez-Santos, Idaira, Meizner, Daniela, Quiroz-Mercado, Hugo, Smith, Jesse M
Format: Article
Language:English
Subjects:
Adult
Aged
Case-Control Studies
Complement Activation - physiology
Complement System Proteins - metabolism
Diabetic Retinopathy - diagnosis
Diabetic Retinopathy - metabolism
Diabetic Retinopathy - surgery
Female
Follow-Up Studies
Humans
Male
Middle Aged
Retina
Vitrectomy
Vitreous Body - metabolism
Vitreous Body - pathology
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Summary:A growing body of evidence points to complement dysregulation in diabetes. Early studies have indicated the presence of complement components inside the eye in patients with diabetic retinopathy, but these data have been confounded by leakage of proteins from the systemic circulation into the vitreous cavity. We took samples of plasma and vitreous from patients with and without proliferative diabetic retinopathy (PDR) and measured levels of 16 complement components as well as albumin. We employed a normalized ratio using local and systemic complement and albumin levels to control for vascular leakage into the vitreous cavity. Before normalizing, we found significantly higher levels of 16 complement components we measured in PDR eyes compared to controls. After normalizing, levels of C4, factor B, and C5 were decreased compared to controls, while C3a and Ba levels were elevated compared to controls. We also found higher ratios of C3a/C3, C5a/C5, and Ba/factor B in PDR eyes compared to controls. We found evidence of local, intraocular activation of C3, C5, and factor B. The normalized data suggest involvement of the alternative complement pathway. By showing activation of specific complement components in PDR, this study identifies targets for diagnostic and therapeutic potential.
ISSN:1552-5783
0146-0404
1552-5783
DOI:10.1167/iovs.61.11.39