Evaluating the protective effects of dexamethasone and electrospun mesh combination on primary human mixed retinal cells under hyperglycemic stress

Abstract

Chronic inflammation is a leading cause of neurodegeneration and vision loss in hyperglycemia-associated conditions such as diabetic retinopathy. Corticosteroid injections are widely used for treatment but suffer from limitations such as rapid drug clearance, short drug half-lives and frequent administration. While drug release from biomaterial carriers can overcome these shortcomings, evaluating the combined effects of corticosteroids and polymeric matrices under hyperglycemic stress is an important step towards aiding translation. In this study, we investigated the effects of dexamethasone (DEX) and electrospun mesh combination on primary human mixed retinal cells under normal and hyperglycemic culture conditions. DEX-incorporated poly(lactide-co-glycolide) (PLGA) meshes were prepared and characterized for architecture, chemistry, drug distribution and in vitro release. The meshes exhibited cumulative in vitro drug release of 39.5 % over 2 months at a near constant rate. Under normal culture conditions, DEX-PLGA meshes promoted significantly higher viability of mixed retinal cells than the control groups but without adverse phenotypic activation. Under hyperglycemic conditions, DEX supplementation resulted in higher viability than the control, although the highest viability was achieved only when DEX was added to cells cultured on PLGA fibers. The combination of DEX and PLGA fibers also promoted higher mRNA expression of the antioxidant GSH under hyperglycemia. Importantly, the largest reduction in the production of pro-inflammatory cytokines viz., MMP-9, IL-6, IL-8 and VEGF-R1 was observed for the DEX and PLGA combination. Our study reveals a combined effect of DEX and electrospun fibers in combating hyperglycemia-driven pro-inflammatory responses, which can aid the development of DEX-loaded electrospun implants for diabetes-driven retinal conditions.