Scott W. McPherson, Ph.D.
Adjunct Assistant Professor
Department of Ophthalmology and Visual Neurosciences
University of Minnesota
Room 482A, Lions Research Building
2001 6th St. SE
Minneapolis, MN. 55455
Academic Background: Dr. McPherson received his Ph.D. in Microbiology from the University of Minnesota in 1993. He then joined the laboratory of Dr. Dale Gregerson, Department of Ophthalmology, University of Minnesota. Dr. McPherson was appointed Adjunct Assistant Professor in 2021.
Program in Ocular Immunology. The research program in ocular immunology was begun by Dr. Dale Gregerson in 1983 and was led by him until his retirement in 2019. Dr. Gregerson is now Professor Emeritus, Department of Ophthalmology and Visual Neurosciences. Dr. McPherson now heads the research program in ocular immunology. The work is currently supported by an RO1 grant from the National Eye Institute (EY033328-01) and by department and UMN startup funds.
Your Eyes and Your Immune System: The Connection
Your immune system does more than “fight germs” -- it maintains the healthy “status quo” or homeostasis of all tissues in your body. Immunologist have learned that certain tissues can and need to locally control immune responses to best take advantage of the protective functions of the immune system while limiting inflammation and/or cytotoxicity often associated with the clearance of pathogens or non-self-entities. Tissues with this ability are termed immune privileged. Given the fragile and non-regenerative nature of many cells in the eye, particularly the retina, and the need to maintain the clarity of the central visual axis (cornea, lens, vitreous) to the retina, it is easy to see why immunoregulation within the eye is crucial to one’s health and well-being. The eye is the body’s paradigm tissue for local control and alteration of immune responses. Nearly all described mechanisms of immune regulation have been demonstrated to occur within the eye. In fact, some were first elucidated by studying ocular immune responses while others have been shown to be unique to the eye. The eye is uniquely suited to study immune privilege. We can specifically alter or manipulate the ocular environment to test ideas about local immune regulation and often simply just need to look into the eye to see what is going on.
Ocular Immunology: Current and Future Research
There are several emerging narratives in retinal immunology that we are currently exploring. First is the idea that retinal innate immune cells, generally referred to as microglia and thought of as a single entity, are actually composed of cellular subsets. Each of these subsets while phenotypically similar, respond differently to stimuli and carry out distinct functions crucial to both retinal homeostasis and retinal autoimmunity. Related to this is the idea that structural cells of the retina (vascular epithelial cells, astrocytes, retinal pigment epithelium) contribute to retinal immune privilege, but which cells and how they contribute remains to be deciphered. Second is the recent immunological concept that T cell anergy (a state of functional unresponsiveness in T cell) is not a passive process but rather an active process that is both necessary and complementary to regulatory T cell function in maintaining immune homeostasis. However, the importance of T cell anergy in retinal immune homeostasis has remained unexplored. Finally, is the idea that the eye, particularly the retina, is an ideal system for elucidating the mechanisms of tissue specific autoimmunity and how to control it. We believe that local manipulations of antigen presentation and regulatory T cell generation could be clinically useful therapies against retinal inflammation, a leading cause of blindness. While much has been learned about controlling autoimmunity, these advances have been primarily at the systemic level and therapies that ameliorate autoimmunity at the local or organ-specific level, thus free of systemic side effects, have remained elusive.
A paucity of phenotypic markers along with the fact that the retinal microenvironment compels newly arriving innate immune cells to be the equivalent of endogenous microglia has made identifying microglial subsets difficult. In future studies, we would like to apply advanced genomics, particularly single cell expression profiling, to identify retinal microglia subsets. This type of analysis will provide much greater information than available by expression studies using bulk mRNA or flow cytometry, allowing us to identify multiple subsets of microglia at steady state physiology and how the balance and function of these subsets change in response to stimuli. Although we have demonstrated that antigen specific regulatory T cells develop in response to that antigen being expressed in the retina, whether non-retinal antigen specific regulatory T cells are important for retinal immune homeostasis remains unanswered. We would like to combine retinal antigen specific T cell receptor transgenic mice, specific retinal antigen knock-out mice, and mice with regulatory T cells that are labeled and depletable to investigate this question. The results would be applicable to not only retinal immunology but to how regulatory T cells function in general in maintaining immune tolerance and limiting antigen specific T cell responses.
Parabiosis reveals the correlation between the recruitment of circulating antigen presenting cells to the retina and the induction of spontaneous autoimmune uveoretinitis. McPherson SW, Heuss ND, Abedin M, Roehrich H, Pierson MJ, Gregerson DS. J Neuroinflammation. 2022 Dec 9;19(1):295. doi: 10.1186/s12974-022-02660-2.PMID: 36494807
The retinal environment induces microglia-like properties in recruited myeloid cells. McPherson SW, Heuss ND, Lehmann U, Roehrich H, Abedin M, Gregerson DS. J Neuroinflammation. 2019 Jul 20;16(1):151. doi: 10.1186/s12974-019-1546-9.PMID: 31325968
Optic nerve as a source of activated retinal microglia post-injury. Heuss ND, Pierson MJ, Roehrich H, McPherson SW, Gram AL, Li L, Gregerson DS. Acta Neuropathol Commun. 2018 Jul 23;6(1):66. doi: 10.1186/s40478-018-0571-8.PMID: 30037353
Retinal antigen-specific regulatory T cells protect against spontaneous and induced autoimmunity and require local dendritic cells. McPherson SW, Heuss ND, Pierson MJ,
Gregerson DS. J Neuroinflammation. 2014 Dec 11;11:205. doi: 10.1186/s12974-014-0205-4.PMID: 25498509
Retinal dendritic cell recruitment, but not function, was inhibited in MyD88 and TRIF deficient mice. Heuss ND, Pierson MJ, Montaniel KR, McPherson SW, Lehmann U, Hussong SA, Ferrington DA, Low WC, Gregerson DS. J Neuroinflammation. 2014 Aug 13;11:143. doi: 10.1186/s12974-014-0143-1.PMID: 25116321
Local "on-demand" generation and function of antigen-specific Foxp3+ regulatory T cells. McPherson SW, Heuss ND, Gregerson DS. J Immunol. 2013 May 15;190(10):4971-81. doi: 10.4049/jimmunol.1202625. Epub 2013 Apr 12.PMID: 23585681
A complete list of Dr. McPherson’s publications can be found at:https://www.ncbi.nlm.nih.gov/sites/myncbi/1RoYtXvjIzOYmq/collections/60750244/public/