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Peeking into Sigma-1 Receptor Functions Through the Retina

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Sigma Receptors: Their Role in Disease and as Therapeutic Targets

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 964))

Abstract

This review discusses recent advances towards understanding the sigma-1 receptor (S1R) as an endogenous neuro-protective mechanism in the retina , a favorable experimental model system. The exquisite architecture of the mammalian retina features layered and intricately wired neurons supported by non-neuronal cells. Ganglion neurons, photoreceptors , as well as the retinal pigment epithelium, are susceptible to degeneration that leads to major retinal diseases such as glaucoma , diabetic retinopathy , and age-related macular degeneration (AMD), and ultimately, blindness. The S1R protein is found essentially in every retinal cell type, with high abundance in the ganglion cell layer. Ultrastructural studies of photoreceptors, bipolar cells, and ganglion cells show a predominant localization of S1R in the nuclear envelope. A protective role of S1R for ganglion and photoreceptor cells is supported by in vitro and in vivo experiments. Most recently, studies suggest that S1R may also protect retinal neurons via its activities in Müller glia and microglia. The S1R functions in the retina may be attributed to a reduction of excitotoxicity, oxidative stress , ER stress response, or inflammation. S1R knockout mice are being used to delineate the S1R-specific effects. In summary, while significant progress has been made towards the objective of establishing a S1R-targeted paradigm for retinal neuro-protection , critical questions remain. In particular, context-dependent effects and potential side effects of interventions targeting S1R need to be studied in more diverse and more clinically relevant animal models.

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Acknowledgement

This work was supported by the National Eye Institute grant R01EY022678 and a Morgridge Institute for Research & the James Christenson Estate Macular Degeneration Research Award (to L-W Guo), and P30EY016665 and S10OD018221 (to the University of Wisconsin Vision Core). The project was also supported by the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant UL1TR000427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

We thank Drs. Miles L. Epstein and Arnold E. Ruoho for critical comments. We also thank Dr. Laura Hogan at the University of Wisconsin Institute for Clinical & Translational Research (ICTR) for editing and proof-reading.

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Authors and Affiliations

  1. Department of Surgery and McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, 5151 Wisconsin Institute for Medical Research, 1111 Highland Ave, 53705, Madison, WI, USA

    Timur A. Mavlyutov & Lian-Wang Guo

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  1. Timur A. Mavlyutov
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  2. Lian-Wang Guo
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Editors and Affiliations

  1. Departments of Cellular Biology and Anatomy and Ophthalmology and the James and Jean Culver Vision Discovery Institute, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

    Sylvia B. Smith

  2. Cellular Pathobiology Section, Integrative Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, US Department of Health and Human Services, Baltimore, Maryland, USA

    Tsung-Ping Su

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Mavlyutov, T.A., Guo, LW. (2017). Peeking into Sigma-1 Receptor Functions Through the Retina. In: Smith, S., Su, TP. (eds) Sigma Receptors: Their Role in Disease and as Therapeutic Targets. Advances in Experimental Medicine and Biology, vol 964. Springer, Cham. https://doi.org/10.1007/978-3-319-50174-1_19

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