Yusuke Murakami 교수

Retinitis pigmentosa comprises a group of inherited retinal photoreceptor degenerations that lead to progressive loss of vision. Although in most cases rods, but not cones, harbor the deleterious gene mutations, cones do die in this disease, usually after the main phase of rod cell loss. Rod photoreceptor death is characterized by apoptotic features. In contrast, the mechanisms and features of subsequent nonautonomous cone cell death remain largely unknown. In this study, we show that receptor-i

Both the superficial and deep layers of the parafoveal microvasculature are attenuated in RP and correlated with reduced central visual function. The foveal microvasculature, especially in the deep layer, was relatively preserved until mild-to-moderately advanced stages.

An imbalance between the production of reactive oxygen species (ROS) and anti-oxidant capacity results in oxidative injury to cellular components and molecules, which in turn disturbs the homeostasis of cells and organs. Although retinitis pigmentosa (RP) is a hereditary disease, non-genetic biological factors including oxidative stress also modulate or contribute to the disease progression. In animal models of RP, the degenerating retina exhibits marked oxidative damage in the nucleic acids, pr

Photoreceptor cell death is the terminal event in a variety of retinal disorders including age-related macular degeneration, retinitis pigmentosa, and retinal detachment. Apoptosis has been thought to be the major form of cell death in these diseases, however accumulating evidence suggests that another pathway, programmed necrosis is also important. Recent studies have shown that, when caspase pathways are blocked, receptor interacting protein (RIP) kinases promote necrosis and overcome apoptosi

Decreased macular blood flow was associated with reduced macular visual sensitivity in patients with RP. Although the cause-effect relationships remain to be elucidated, these findings suggest that vascular defects may be involved in the pathogenesis of RP such as central vision loss.

Lentiviral vectors are promising tools for the treatment of chronic retinal diseases, including age-related macular degeneration (AMD), as they enable stable transgene expression. On the other hand, Sendai virus (SeV) vectors provide the unique advantage of rapid gene transfer. Here we show that novel simian immunodeficiency viral vectors pseudotyped with SeV envelope proteins (SeV-F/HN-SIV) achieved rapid, efficient, and long-lasting gene transfer in the mouse retina. Subretinal exposure to SeV

Retinitis pigmentosa (RP) comprises a group of inherited retinal degenerations, resulting from rod and cone photoreceptor cell death. Genetic studies have identified mutations in more than 50 genes—most of which encode rod-related molecules—that are associated with RP. Although rod cells that harbor the deleterious mutations are expected to die, it remains a puzzle why cone cells also die in this disease, subsequent to rod degeneration. Because the loss of cone-mediated vision is the most debili

Peripheral inflammatory response may be activated and serum IL-8 levels are associated with central vision in patients with RP.

Oxidative stress is implicated in various neurodegenerative disorders, including retinitis pigmentosa (RP), an inherited disease that causes blindness. The biological and cellular mechanisms by which oxidative stress mediates neuronal cell death are largely unknown. In a mouse model of RP (rd10 mice), we show that oxidative DNA damage activates microglia through MutY homolog-mediated (MUYTH-mediated) base excision repair (BER), thereby exacerbating retinal inflammation and degeneration. In the e