Docosanoid signaling modulates corneal nerve regeneration: effect on tear secretion, wound healing, and neuropathic pain

Autor: Thang Luong Pham, Haydee E. P. Bazan
Rok vydání: 2020
Předmět:
0301 basic medicine
HDHA
hydroxy-DHA
030204 cardiovascular system & hematology
Pharmacology
Biochemistry
NPD1
neuroprotectin D1
Cornea
dry eye
0302 clinical medicine
Endocrinology
stereoisomer of resolvin D6
Tear secretion
LOX
lipoxygenase
PEDF
pigment epithelium-derived factor
DE
dry eye
RvD6
resolvin D6
docosahexaenoic acid
medicine.anatomical_structure
Neuropathic pain
BDNF
brain-derived neurotrophic factor
Docosanoid
Thematic Review Series: Seeing 2020: Lipids and Lipid-Soluble Molecules in the Eye
neuroprotectin D1
pigment epithelium-derived factor
NGF
nerve growth factor
PEDF-R
pigment epithelium-derived factor receptor
QD415-436
Corneal ulceration
PRK
photorefractive keratectomy
03 medical and health sciences
omega 3 fatty acids
medicine
cell signaling
SP
substance P
Brain-derived neurotrophic factor
business.industry
Thematic Review Series
Cell Biology
lipoxygenase
eye diseases
DED
dry eye disease
COX
cyclooxygenase
030104 developmental biology
Nerve growth factor
TG
trigeminal ganglia
gene expression
phospholipase A2
sense organs
Wound healing
business
Zdroj: Journal of Lipid Research
Journal of Lipid Research, Vol 62, Iss, Pp 100033-(2021)
ISSN: 1539-7262
Popis: The cornea is densely innervated, mainly by sensory nerves of the ophthalmic branch of the trigeminal ganglia (TG). These nerves are important to maintain corneal homeostasis, and nerve damage can lead to a decrease in wound healing, an increase in corneal ulceration and dry eye disease (DED), and neuropathic pain. Pathologies, such as diabetes, aging, viral and bacterial infection, as well as prolonged use of contact lenses and surgeries to correct vision can produce nerve damage. There are no effective therapies to alleviate DED (a multifunctional disease) and several clinical trials using ω-3 supplementation show unclear and sometimes negative results. Using animal models of corneal nerve damage, we show that treating corneas with pigment epithelium-derived factor plus DHA increases nerve regeneration, wound healing, and tear secretion. The mechanism involves the activation of a calcium-independent phospholipase A2 that releases the incorporated DHA from phospholipids and enhances the synthesis of the docosanoids, neuroprotectin D1 (NPD1) and a new resolvin stereoisomer, resolvin D6i (RvD6i). NPD1 stimulates the synthesis of brain-derived neurotrophic factor, nerve growth factor, and semaphorin 7A. RvD6i treatment of injured corneas modulates gene expression in the TG resulting in enhanced neurogenesis, decreased neuropathic pain, and increased sensitivity. Taken together, these results represent a promising therapeutic option to reestablish the homeostasis of the cornea.
Databáze: OpenAIRE
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