Association of metabotropic glutamate receptor 7 gene with nicotine dependence in a Chinese Han population: A cross-sectional candidate-gene association study.

Retinitis pigmentosa (RP) is a group of complex, multifactorial, degenerative retinal diseases characterized by the loss of photoreceptors and retinal pigment epithelium (RPE), leading to blindness. RP is one of the most common retinal degeneration diseases worldwide, affecting more than 2.5 million people. Currently, no effective prevention or therapies for this devastating disease are clinically available. Over the past several decades, studies have demonstrated that mutations in more than 100 genes are associated with RP. Although damage to photoreceptors and RPE cells contributes to RP, the specific mechanisms that render photoreceptors and RPE cells more vulnerable to damage in patients with RP have not been identified. Therefore, investigations into the pathophysiological mechanisms of RP are urgently needed to develop prevention strategies and treatments for this destructive disease. Reactive oxygen species (ROS) are involved in the pathogenesis of RP. Mitochondrial damage generates ROS, which may trigger mitochondrial dysfunction and amplify ROS production. Mitochondria perform a variety of tasks, including the generation of adenosine triphosphate (ATP), Ca buffering, and epigenetic signaling. Mitochondrial dysfunction is a crucial factor in a variety of neurodegenerative diseases. Impaired mitochondria and energy metabolism disorders are significant features of aging and age-related neurodegeneration, including Alzheimer’s disease and Parkinson’s disease. The retina contains abundant mitochondria, which support normal retinal physiological functions; mitochondria are involved in phototransduction in RPE cells and mediate photoelectric signal transduction in retinal neuroepithelial cells. Retinas are exposed to a high-oxygen environment, which is exacerbated by the loss of rods in RP; these conditions create a hyperoxic environment that is hostile to the remaining cells. Mitochondrial dysfunction may be involved in retinal degeneration in RP, and augmenting the mitochondrial damage defense systems may protect the retina in RP and other inherited retinal dystrophies. Nicotinamide adenine dinucleotide (NAD+) is a coenzyme for dehydrogenase enzymes that perform reduction-oxidation (redox) reactions, connecting glycolysis and the citric acid cycle to oxidative phosphorylation via the electron transport chain (ETC). Thus, NAD+ homeostasis plays a crucial role in maintaining mitochondrial function. Previous neurodegeneration studies suggest that perturbations in NAD+ homeostasis contribute to retinal neurodegeneration. In the Wds mouse model, a chimeric protein capable of enhancing NMNAT1 enzymatic activity and maintaining NAD homeostasis significantly delayed the progression of degenerative lesions induced by neuronal axonal injury; this chimeric protein contributed to the repair and growth of neuronal axons. Glaucoma-prone mice exhibited retinal NAD+ deficiency with age, leading to mitochondrial abnormalities and, ultimately, retinal neuronal dysfunction; the retinal neuronal dysfunction was attenuated by supplementation with the NAD+ precursor nicotinamide (vitamin B3). Photoreceptors are highly specialized neurons that may rely on NAD+ homeostasis for survival and function. However, the contribution of the NAD+-mitochondria pathway to the development of RP and dysfunction in RPE cells and photoreceptors is unclear and is the focus of our current research.