Glucocorticoids: Structure, Signaling and Molecular Mechanisms in the Treatment of Diabetic Retinopathy and Diabetic Macular Edema
X. Zhang, N. Wang, A.P. Schachat, S. Bao and M.C. Gillies
Affiliation: Beijing Institute of Ophthalmology, Tongren Eye Centre, Tongren Hospital, Ophthalmology & Visual Sciences Key Lab，Capital Medical University, 100730, P.R. China.
Keywords: Diabetic retinopathy, glucocorticoids, glucocorticoid receptors, neuronal protection.
Diabetic retinopathy (DR) is one of the leading causes of blindness in the working population
worldwide. Vascular leakage, angiogenesis and neuronal degeneration are key features of DR. Current
effective interventions for DR include treatment of systemic risk factors such as elevated blood glucose, blood
pressure and dyslipidemia. Ocular treatments include vascular endothelial growth factor A (VEGF-A) inhibitors,
laser photocoagulation and surgery. While anti-VEGF therapy has become as first-line treatment for diabetic
macular edema (DME) that causes reduced vision, intravitreal glucocorticoids also have been shown to be
efficacious in this situation. It has been reported that all the major pathological processes of DR are susceptible
to glucocorticoid treatment. The effects of glucocorticoids on vascular leakage and angiogenesis may be
mediated through their well established anti-inflammatory role. Alternatively, glucocorticoids may affect other
mechanisms known to be activated in DR. Potential mechanisms for the anti-inflammatory effects of
glucocorticoids include blockage of cytokine production and inhibition of leukocyte adhesion induced by VEGF-A.
Glucocorticoids decrease the expression of VEGF-A directly, and increase the production, or decrease
phosphorylation, of tight junction-associated proteins. Glucocorticoids have also been shown to be
neuroprotective, in contrast to VEGF-A inhibitors which animal studies suggest may be neurotoxic. This review
outlines the biological properties of synthetic glucocorticoids, with particular emphasis on the potential beneficial
effect of combining glucocorticoids with anti-VEGF treatment for DME and DR.
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