The healthy eye possesses a unique physiological and evolutionary adaptation that modifies the expression of immunity. This physiological adaptation is part of ocular immune privilege. The physiological role of immune privilege is to impart upon the eye immune protection that avoids the destructive side effects of immunogenic inflammation. Immunogenic inflammation associated with hypersensitivity reactions can grossly distort the visual axis resulting in blindness. Within the immune privileged ocular microenvironment, there are active mechanisms of immunoregulation and immunosuppression. This ocular system of immunoregulation and immunosuppression not only suppresses immunogenic inflammation, but also actively manipulates immunity to make the immune response itself immunosuppressive. By understanding the mechanism of ocular immunity, it will be possible to induce an immune response that promotes the elimination of pathogens and tumors without the consequences of immunogenic inflammation, prevent or cure ocular and other autoimmune diseases, and induce immunity that promotes acceptance of corneal, retinal, and other tissue transplants. The objectives of this proposal are to identify, characterize, and establish the role of constitutively produced factors that are immunoregulatory and immunosuppressive in the eye. We hypothesize that the such factors suppress the activation of innate and adaptive immunity associated with inflammation, while enhancing or maintaining expression of the characteristics associated with immune regulation or suppression. We will test this hypothesis by demonstrating that the ocular microenvironment promotes the alternative activation and induction of suppressor macrophages, that the ocular microenvironment promotes the induction of effector regulatory T cells, and that the nervous system makes a significant contribution to ocular immunity.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY010752-15
Application #
8091256
Study Section
Anterior Eye Disease Study Section (AED)
Program Officer
Mckie, George Ann
Project Start
1995-04-01
Project End
2013-03-31
Budget Start
2011-04-01
Budget End
2013-03-31
Support Year
15
Fiscal Year
2011
Total Cost
$349,201
Indirect Cost
Name
Boston University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Taylor, A W; Dixit, S; Yu, J (2015) Retinal Pigment Epithelial Cell Line Suppression of Phagolysosome Activation. Int J Ophthalmol Eye Sci Suppl 2:1-6
Phan, Toan A; Taylor, Andrew W (2013) The neuropeptides ?-MSH and NPY modulate phagocytosis and phagolysosome activation in RAW 264.7 cells. J Neuroimmunol 260:9-16
Lee, Darren J; Taylor, Andrew W (2013) Both MC5r and A2Ar are required for protective regulatory immunity in the spleen of post-experimental autoimmune uveitis in mice. J Immunol 191:4103-11
Taylor, Andrew W (2013) Alpha-melanocyte stimulating hormone (?-MSH) is a post-caspase suppressor of apoptosis in RAW 264.7 macrophages. PLoS One 8:e74488
Taylor, Andrew W (2012) Primary Open-Angle Glaucoma: A Transforming Growth Factor-ýý Pathway-Mediated Disease. Am J Pathol 180:2201-4
Kawanaka, Norikuni; Taylor, Andrew W (2011) Localized retinal neuropeptide regulation of macrophage and microglial cell functionality. J Neuroimmunol 232:17-25
Taylor, Andrew W; Lee, Darren J (2011) The alpha-melanocyte stimulating hormone induces conversion of effector T cells into treg cells. J Transplant 2011:246856
Lee, Darren J; Taylor, Andrew W (2011) Following EAU recovery there is an associated MC5r-dependent APC induction of regulatory immunity in the spleen. Invest Ophthalmol Vis Sci 52:8862-7
Taylor, Andrew W; Kaplan, Henry J (2010) Ocular immune privilege in the year 2010: ocular immune privilege and uveitis. Ocul Immunol Inflamm 18:488-92
Taylor, Andrew W; Lee, Darren (2010) Applications of the role of ?-MSH in ocular immune privilege. Adv Exp Med Biol 681:143-9

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