Decorin Concentrations in Aqueous Humor of Patients with Diabetic Retinopathy

Abstract

Diabetic retinopathy (DR) is a microvascular complication of diabetes in the retina. Chronic hyperglycemia damages retinal microvasculature embedded into the extracellular matrix (ECM), causing fluid leakage and ischemic retinal neovascularization. Current treatment strategies include intravitreal anti-vascular endothelial growth factor (VEGF) or steroidal injections, laser photocoagulation, or vitrectomy in severe cases. However, treatment may require multiple modalities or repeat treatments due to variable response. Though DR management has achieved great success, improved, long-lasting, and predictable treatments are needed, including new biomarkers and therapeutic approaches. Small-leucine rich proteoglycans, such as decorin, constitute an integral component of retinal endothelial ECM. Therefore, any damage to microvasculature can trigger its antifibrotic and antiangiogenic response against retinal vascular pathologies, including DR. We conducted a cross-sectional study to examine the association between aqueous humor (AH) decorin levels, if any, and severity of DR. A total of 82 subjects (26 control, 56 DR) were recruited. AH was collected and decorin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Decorin was significantly increased in the AH of DR subjects compared to controls (p = 0.0034). AH decorin levels were increased in severe DR groups in ETDRS and Gloucestershire classifications. Decorin concentrations also displayed a significant association with visual acuity (LogMAR) measurements. In conclusion, aqueous humor decorin concentrations were found elevated in DR subjects, possibly due to a compensatory response to the retinal microvascular changes during hyperglycemia.

Serum Amyloid A 4 as a Common Marker of Persistent Inflammation in Patients with Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy

“… 41 Decorin, a small leucine-rich proteoglycan, has been demonstrated to play a vital role in constituting the retinal microvasculature structure. 42 Retinol-binding protein 4 (RBP4) is an adipocyte-secreted protein and delivers vitamin A from the liver to RPE. A proteomics study conducted by Lim demonstrated that RBP4 could be used as a novel biomarker and therapeutic measure for nAMD.…”

Damage-Associated Molecular Patterns (DAMPs) in Retinal Disorders

“…Though the exact role of biglycan is not defined in DR, preliminary data suggest its angiogenic and inflammatory properties in DR [ 179 , 180 ]. Decorin concentrations have also been reported to be increased in the plasma of diabetic patients and the aqueous humor of DR patients [ 157 , 158 ]. Interestingly, decorin can be a multifunctional DAMP, acting on TLR2/TLR4 and TGF-β signaling pathways, deploying both pro- and anti-inflammatory effects [ 181 ].…”

“…It is essential to discriminate the deleterious role of the DAMPs (usually long-term), contrary to the innate immune responses initiated in the early stage of the disease progression (protective role). Recently, we found increased aqueous humor decorin concentrations associated with the progression of diabetic retinopathy [ 157 ]. Additionally, the most effective way to target DAMPs in the retina is cell- and location-dependent (intracellular or extracellular).…”