Opium and Opioid Receptors: From the Ancient Times to a Possible Novel Therapeutic Target for Diabetic Retinopathy

Abstract

Opium prescriptions date from the Sumerian era about 8,000 years ago, and they were commonly abused among wounded soldiers during the American Civil and Prussian French wars. With the isolation of morphine in 1805 by Setürner, the synthesis of morphine by Tschudi in 1952 and the manufacturing of synthetic derivatives called opioids, a new era of research began. In normal conditions, the endogenous opioid levels are elevated under stress conditions as a part of adaptive response. This mechanism implies in b-endorphin release, not only from the hypothalamus but also by immune circulating cells as lymphocytes. This system is powerful against pain, ischemic insult and oxidative imbalance protecting the tissues. The recognition of opioid receptors, particularly the delta subtype in retinal tissue, has broadened the potential for clinical applications. In the eye, opioid receptors were demonstrated to be present in optic nerve head, ganglion cells and pigmented epithelium cells. As such, studies have revealed that opioid receptors play a role in the pathogenesis of DR preserving the outer blood retinal barrier and also acting as a retinal neuroprotective agent. In this scenario, the modulation of the opioid receptor in the retina might become an attractive therapeutic target in the treatment of this devastating complication. Thus, this review assesses recent and scarce findings on this topic which deserves to be further investigated