Download Myeloid cells in ocular health and disease

ARVO 2015 Annual Meeting Abstracts
214 Myeloid cells in ocular health and disease - Minisymposium
Monday, May 04, 2015 8:30 AM–10:15 AM
601/603 Minisymposium
Program #/Board # Range: 1341–1345
Organizing Section: Immunology/Microbiology
Program Number: 1341
Presentation Time: 8:30 AM–8:55 AM
Immune Suppressive Myeloid Cells
Suzanne Ostrand-Rosenberg. Biological Sciences, Univ. Maryland
Baltimore County, Baltimore, MD.
Presentation Description: Immune suppressive cells of myeloid
origin accumulate in individuals with a variety of conditions.
These conditions typically involve inflammation, and range from
an inflammatory tumor microenvironment to infection, stress,
and aging. The predominant cell types are myeloid-derived
suppressor cells (MDSC) and type 2 or so-called tumor-associated
macrophages (TAMs). The cells are present at low levels in healthy
and young individuals; however, when elevated, MDSC and TAMs
are profoundly immune suppressive cells that neutralize natural
immunity and impede strategies for activating the immune system
to cancer or infectious diseases. A variety of pro-inflammatory
mediators acting through multiple receptors drive the accumulation of
suppressive cells from myeloid progenitor cells. MDSC are present
in most cancer patients and TAMs infiltrate many solid tumors.
MDSC facilitate tumor progression by inhibiting both the innate
and adaptive immune systems, and also by non-immune effects that
promote angiogenesis and tumor invasion and metastasis. This talk
will review the inflammatory conditions that drive the accumulation
of immune suppressive MDSC and macrophages, describe the
mechanisms used by these cells to suppress anti-tumor immunity,
discuss how MDSC both support and dampen inflammation in the
tumor microenvironment, and review some to the strategies that have
been developed to neutralize undesirable effects of hyper-activated
myeloid cells.
Commercial Relationships: Suzanne Ostrand-Rosenberg,
MedImmune, Inc. (F), Nora Therapeutics, Inc. (F)
Support: NIH RO1 CA84232, NIH RO1 GM021248
Program Number: 1342
Presentation Time: 8:55 AM–9:15 AM
Influence of macrophages on intraocular tumor growth
Kyle C. McKenna. 1Univ. Pittsburgh, Pittsburgh, PA; 2Biology,
Franciscan University of Steubenville, Steubenville, OH.
Presentation Description: Experimentation in a mouse model of
intraocular tumor development which indicates that tumor associated
macrophages contribute to both growth and elimination of intraocular
tumors is described and related to our current understanding of the
immunobiology of uveal melanoma.
Commercial Relationships: Kyle C. McKenna, None
Support: NEI EY018355
Program Number: 1343
Presentation Time: 9:15 AM–9:35 AM
Influence of Myeloid Cells in Corneal Wound Healing
Lars Bellner. Pharmacology, New York Medical College, Valhalla,
NY.
Presentation Description: The heme oxygenase (HO) system has
been implicated in the resolution of inflammation. HO is the ratelimiting enzyme in heme catabolism. It cleaves heme to biliverdin,
carbon monoxide (CO), and iron; biliverdin is subsequently
converted by biliverdin reductase to bilirubin.
Our previous studies have shown that a deficiency in HO activity, as
in the HO-2 null (KO) mice, exacerbates ocular surface inflammation
allowing an acute inflammation to become chronic with the hallmarks
of neovascularization, ulceration, perforation and accumulation of
apoptotic cells.
This presentation will give a description of the impact of heme
oxygenase 2 protein deficiency on the function of infiltrating
neutrophils and macrophages in corneal wound healing from its
initial stage, the inflammatory response, and through the resolution
and repair stages.
Commercial Relationships: Lars Bellner, None
Support: NIH Grant EY06513
Program Number: 1344
Presentation Time: 9:35 AM–9:55 AM
Role of cholesterol metabolism in retinal macrophage function
Rajendra S. Apte. Washington Univ., St. Louis, MO.
Presentation Description: Inability of macrophages to effectively
metabolize cholesterol is a cardinal event in the aging of the immune
system. It is also critical to the pathobiology of diverse diseases of
aging including atherosclerosis and macular degeneration (AMD).
Although genetic studies have been successful in associating innate
immunity and cholesterol metabolism with AMD, the link between
dysregulated cholesterol homeostasis in macrophages and initiation
of AMD is not well understood. Current concepts and data on the
regulation of genes involved in macrophage cholesterol homeostasis
during aging and disease will be presented.
Commercial Relationships: Rajendra S. Apte, Metro Midwest (I),
Washington University (P)
Support: This work was supported by NIH Grant K08EY016139
(RSA), NIH Grant R01EY019287 (RSA), NIH Vision Core Grant
P30EY02687, U.S. Civilian Research and Development Foundation
(RSA, IC), Carl Marshall Reeves and Mildred Almen Reeves
Foundation Inc. Award (RSA), Research to Prevent Blindness Inc.
Career Development Award and RPB Physician Scientist Award
(RSA), International Retina Research Foundation (RSA), American
Health Assistance Foundation (RSA), Lacy Foundation Research
Award (AS), Thome Foundation (RSA) and a Research to Prevent
Blindness Inc. Unrestricted Grant to Washington University.
Program Number: 1345
Presentation Time: 9:55 AM–10:15 AM
Optic Nerve Regeneration and Glaucoma: the Yin and Yang of
Intraocular Inflammation
Larry Benowitz. 1Depts. Neurosurgery and Ophthalmology, Harvard
Medical School, Boston, MA; 2Neurosurgery; Kirby Neurobiology
Center, Boston Children’s Hospital, Boston, MA.
Presentation Description: In glaucoma, retinal ganglion cells
(RGCs) undergo apoptotic death due to axonal damage in the
vicinity of the lamina cribrosa. Mechanical injury to the optic
nerve similarly results in apoptotic death of RGCs and is widely
used as a model to investigate mechanisms underlying RGC loss in
glaucoma. Surprisingly, induction of a limited inflammatory reaction
in the eye enhances RGCs’ ability to survive optic nerve damage
and to regenerate axons well beyond the injury site1. The effects
of inflammation on regeneration are due primarily to the atypical
growth factor oncomodulin (Ocm). Ocm mRNA and protein increase
markedly in the eye following the induction of an inflammatory
reaction, and the role of Ocm in mediating the pro-regenerative
effects of inflammation have been established by gain- and loss-offunction studies2-5. Combining intraocular inflammation with cAMP
elevation and pten gene deletion enables some RGCs to regenerate
axons the full length of the optic nerve, reinnervate central target
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
areas, and restore simple visual responses6. Although activated
neutrophils and macrophages both express high levels of Ocm,
immunodepletion studies show that neutrophils represent the more
biologically relevant source5. In animal models of glaucoma, in
contrast, inflammation has a strongly negative effect. Elevation of
intraocular pressure, either by episcleral vein cauterization or lasermediated angle closure, leads to a marked increase in the chemokine
TNF-a in the eye, activation of microglia at the optic nerve head, and
delayed loss of RGCs. Deleting the gene for TNF-a or the TNFR2
receptor, immune-depletion of TNF-a, or systemic injections of
Etanercept, a soluble decoy receptor for TNF-a, greatly increase RGC
survival in animal models of glaucoma despite persistent elevation of
intraocular pressure7,8. Thus, inflammation can have either a strongly
deleterious or a strongly supportive effect on RGCs depending on the
injury model and the type of inflammatory cells that is activated.
1
Yin et al., J Neurosci 23, 2284 (2003); 2Yin et al., Nat Neurosci 9,
843 (2006); 3Yin et al., Proc Natl Acad Sci U S A 106, 19587 (2009);
4
Kurimoto et al., J Neurosci 30, 15654 (2010); 5Kurimoto et al., J
Neurosci 33, 14816 (2013); 6de Lima et al., Proc Natl Acad Sci U S
A 109, 9149 (2012); 7Nakazawa et al., J Neurosci 26, 12633 (2006);
8
Roh et al., PLoS One 7, e40065 (2012).
Commercial Relationships: Larry Benowitz, Boston Children’s
Hospital (R)
Support: NIH/NEI EY05690; Dr. Miriam and Sheldon G. Adelson
Medical Research Foundation
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].