Abstract
Inflammation is a powerful immune countermeasure to tissue damage and infection. The inflammatory response is complex and requires the involvement of myriad signaling pathways and metabolic processes, all governed by a multitude of regulatory systems. Although inflammation is a vital defense against tissue injury and a necessary step in tissue healing, the mechanisms which modulate the initiation, intensity, and duration of this innate immune response can malfunction and result in inappropriate or out-of-control inflammation, even in the absence of an appropriate stimulus. Though the human eye exists in an immune-privileged microenvironment, it is not spared from this. The eye is neither devoid of immune cells nor is it fully sequestered from systemic immune responses, and is therefore fully capable of ruining itself through localized inflammatory dysfunction and systemic inflammatory disease (Taylor AW, Front Immunol 7:37, 2016; Zhou R, Caspi RR, Biol Rep 2, 2010). In fact, a wide range of ocular inflammatory diseases exist and are major causes of blindness in humans. Advances in the understanding of inflammatory processes have revealed new key pathways and molecular factors involved in the mechanisms of inflammation. Lipids and sphingolipids are increasingly being recognized as having important signaling roles in the pathophysiology of ocular inflammatory diseases. What follows below is a discussion of fundamental inflammatory processes, the place of sphingolipids as mediators of said processes, brief descriptions of major inflammatory ocular diseases, and new findings implicating sphingolipids in their pathogenesis.
Keywords
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Abbreviations
- AMD:
-
age-related macular degeneration
- C1P:
-
ceramide 1-phosphate
- Cer:
-
ceramide
- CLRs:
-
C-type lectin receptors
- COX2:
-
cyclooxygenase 2
- DAMPs:
-
Damage-Associated Molecular Patterns
- DM:
-
diabetes mellitus
- DR:
-
diabetic retinopathy
- GlcCer:
-
glucosylceramide
- ICAM-1:
-
Intercellular adhesion molecule 1
- IOP:
-
intraocular pressure
- IRFs:
-
Interferon regulatory factors
- LacCer:
-
lactosylceramide
- LPS:
-
lipopolysaccharide
- MAPK:
-
Mitogen-activated protein kinase
- MCP1:
-
monocyte chemoattractant protein 1
- MS:
-
Multiple Sclerosis
- NLR:
-
NOD-like receptors
- NPDR:
-
Nonproliferative diabetic retinopathy
- PAMPs:
-
Pathogen-Associated Molecular Patterns
- PDR:
-
proliferative diabetic retinopathy
- PRR:
-
Pattern Recognition Receptors
- PVD:
-
posterior vitreous detachment
- RGC:
-
retinal glial cell
- RIP1:
-
Receptor interacting protein-1
- RLRs:
-
Retinoic acid-inducible gene (RIG)-I-like receptors
- RPE:
-
retinal pigmented epithelial
- S1P:
-
sphingosine 1-phosphate
- S1PR2:
-
S1P receptor 2
- NF-κB:
-
Nuclear factor-κB
- Sph:
-
Sphingosine
- TFLL:
-
tear film lipid layer
- TLRs:
-
Toll-like receptors
- VCAM-1:
-
Vascular cell adhesion molecule 1
- VEGF:
-
Vascular endothelial growth factor
- VLC:
-
very long chain
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Acknowledgements
The authors acknowledge the support of the National Eye Institute grants [EY022071, EY025256, EY021725], and grants from Foundation Fighting Blindness Inc., USA and Research to Prevent Blindness Inc., USA.
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Grambergs, R., Mondal, K., Mandal, N. (2019). Inflammatory Ocular Diseases and Sphingolipid Signaling. In: Stiban, J. (eds) Bioactive Ceramides in Health and Disease. Advances in Experimental Medicine and Biology, vol 1159. Springer, Cham. https://doi.org/10.1007/978-3-030-21162-2_8
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