Reverse Translational Study of Fenofibrate's Observed Effects in Diabetes-Associated Retinopathy
1Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, Arkansas, USA.
Abstract:
Clinical trials suggest that fenofibrate reduces the progression of retinopathies in patients with type 2 diabetes. Furthermore, patients with retinopathies have elevated levels of inflammatory chemokines and dysfunctional retinal angiogenesis. Therefore, we investigated the effects of fenofibrate on the production of inflammatory chemokines and genes associated with angiogenesis. Retinal pigment epithelial cells (RPECs) were cultured with IL-1β and fenofibrate ranging from 1-50 μM. ENA-78, IL-8, and RANTES were measured in cell culture by ELISA. ENA-78, ABCA1, and ABCG1 gene expression were tested by RT-PCR. IL-1β significantly induced the production of ENA-78, IL-8, and RANTES. Fenofibrate at concentrations of 25-50 uM blunted the IL-1β induced production of ENA-78 (p < 0.05) with no significant effects on RANTES and IL-8. Fenofibrate also reduced the expression of the ENA-78 gene as well as ABCA1 and ABCG1, which are genes involved in angiogenesis. Fenofibrate decreases ENA-78 production and ABCA1/ABCG1 gene expression in RPECs.
Insights
Fenofibrate can reduce inflammatory chemokines and genes linked to abnormal blood vessel growth in retinal cells. This suggests a potential therapeutic role for fenofibrate in managing diabetic retinopathy.
Area of Science:
- Ophthalmology
- Endocrinology
- Molecular Biology
Background:
- Diabetic retinopathy is a leading cause of vision loss.
- Retinopathies involve increased inflammatory chemokines and aberrant retinal angiogenesis.
- Fenofibrate shows promise in reducing diabetic retinopathy progression.
Purpose of the Study:
- Investigate fenofibrate's effects on inflammatory chemokines.
- Examine fenofibrate's impact on genes associated with angiogenesis in retinal cells.
Main Methods:
- Retinal pigment epithelial cells (RPECs) were treated with IL-1β and varying concentrations of fenofibrate.
- Chemokine production (ENA-78, IL-8, RANTES) was measured using ELISA.
- Gene expression of ENA-78, ABCA1, and ABCG1 was analyzed via RT-PCR.
Main Results:
- IL-1β significantly increased ENA-78, IL-8, and RANTES production.
- Fenofibrate (25–50 μM) significantly reduced IL-1β-induced ENA-78 production.
- Fenofibrate decreased ENA-78 gene expression and expression of angiogenesis-related genes ABCA1 and ABCG1.
Conclusions:
- Fenofibrate mitigates the production of specific inflammatory chemokines in RPECs.
- Fenofibrate downregulates genes involved in angiogenesis, potentially impacting retinal vascularization.
- These findings support fenofibrate's potential therapeutic benefit in diabetic retinopathy by targeting inflammation and angiogenesis.
