Title:Non-Analgesic Effects of Opioids: Neuroprotection in the Retina
Volume: 18
Issue: 37
Author(s): Shahid Husain, Yasir Abdul and David E. Potter
Affiliation:
Keywords:
Opioid, retina, ischemia, TNF-α, opioid-receptor, blood flow, blindness, diabetic retinopathy, glaucoma, retinal artery occlusion.
Abstract: Inadequate blood flow in the retina (ischemia) is a common cause of visual impairment and blindness. Retinal ischemia plays a
pivotal role in a number of ocular degenerative diseases such as diabetic retinopathy, glaucoma, and retinal artery occlusion. The sequence
of events by which ischemia leads to retinal degeneration are not completely understood, but likely involve both necrotic and
apoptotic processes. A variety of diverse chemical mediators (e.g., glutamate, oxygen free-radical, nitric oxide, and proinflammatory cytokines)
have been implicated as participants in ischemic retinal injury. In the eye, experimental and/or clinical evidence has suggested
roles for endogenous opioids and their receptors in the regulation of iris function, aqueous humor dynamics, corneal wound healing, and
retinal development and neuroprotection. In numerous vital organs, opioid receptor activation prior to ischemia or severe hypoxia is neuroprotective.
Recently, activation of opioid-receptors, particularly δ-opioid-receptors (DOR), has been demonstrated to suppress several
steps in the deleterious cascade of events during ischemic/hypoxic stress. In providing neuroprotection against ischemia, opioid-receptor
activation appears to block proinflammatory cytokines, such as TNF-α, and glutamate excitotoxicity. Depending on duration and severity
of cellular stress, DOR activation can trigger different mechanisms at multiple levels to preserve neuronal survival, including: stabilized
ionic homeostasis, augmented pro-survival signaling (e.g., PKC, ERK, PI3K/Akt) and enhanced anti-oxidative capacity. This review will
summarize the potential roles of opioids in protecting the viability of ocular tissues. Special emphasis will be focused on enhancing the
understanding of the molecular mechanisms of opioid actions in protecting the retina against ischemic/hypoxic injury.
