All-Trans Retinoic Acid in Rodent Models of Autoimmune Diabetes: Clinical Potential of Targeted Drug Delivery.

Abstract

Type 1 diabetes (T1D) is a chronic disease characterized by the relentless autoimmune destruction of insulin-producing pancreatic beta cells (β cells). Approximately 9.5 million people worldwide live with T1D; 1.9 million are under 20 years old. There is no cure and there are few effective treatments, making novel therapies desperately needed. All-trans retinoic acid (ATRA) has demonstrated promise in preventing and even ameliorating T1D, particularly in various rodent T1D models. The benefits are thought to be mediated by influences on T cells, particularly regulatory (Treg) and autoreactive effector T cells. Intriguingly, ATRA may also directly contribute to the differentiation and maintenance of pancreatic β cells. This mini review will focus on experiences with ATRA in rodent models of T1D, including measures of efficacy, Treg expansion, reduction of autoreactive effector T-cell activity and oxidative stress, and, perhaps most promisingly, preservation and stimulation of pancreatic β cells. We will then discuss the clinical potential of ATRA in T1D, including targeted drug delivery strategies to deliver ATRA locally to the relevant immune microenvironment, limiting its systemic exposure, reducing toxic side effects, and enhancing efficacy.