Altered expression of neurotransmitter receptors and neuromediators in vernal keratoconjunctivitis.
BACKGROUND
There is growing evidence that autonomic innervation is involved in the pathogenesis of mucus hypersecretion, goblet cell hyperplasia, and conjunctival hyperreactivity.


OBJECTIVE
To determine the expression of neurotransmitters and neurotransmitter receptors in vernal keratoconjunctivitis (VKC) tissues to evaluate whether neurogenic inflammation plays a role in this ocular atopic-related disorder.


METHODS
Biopsy specimens of upper tarsal conjunctiva from 8 VKC patients with active inflammation and from 4 healthy subjects were processed for immunohistochemistry using anti-M1, anti-M2, and anti-M3 muscarinic receptors; beta1-adrenergic receptor; vasoactive intestinal peptide; nerve growth factor; and protein gene product 9.5, a marker of nerve fibers.


RESULTS
In the conjunctival epithelium of VKC patients, M1 muscarinic receptor, nerve growth factor, and protein gene product 9.5 expression were decreased, whereas M2 and M3 muscarinic receptors and beta1-adrenergic receptor were irregularly distributed, compared with control subjects. Neurotransmitter receptors and vasoactive intestinal peptide expression were increased in the substantia propria-localized infiltrate of VKC compared with healthy tissue. Nerve growth factor and protein gene product 9.5 staining was also enhanced in the conjunctival stroma of VKC vs healthy conjunctiva.


CONCLUSIONS
The inflamed conjunctiva of VKC patients demonstrated an obvious alteration in muscarinic and beta1-adrenergic receptor, vasoactive intestinal peptide, protein gene product 9.5, and nerve growth factor expression. These results substantiate the involvement of an autonomic dysfunction in the pathogenesis of VKC.
Motterle
Laura
L
Department of Neuroscience, Ophthalmology Unit, University of Padova, Padova, Italy.
Diebold
Yolanda
Y
Enríquez de Salamanca
Amalia
A
Saez
Victoria
V
Garcia-Vazquez
Carmen
C
Stern
Michael E
ME
Calonge
Margarita
M
Leonardi
Andrea
A
D000293:Adolescent; D001341:Autonomic Nervous System / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D003228:Conjunctiva / Q000378:metabolism; D003233:Conjunctivitis, Allergic / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009412:Nerve Fibers / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D015415:Biomarkers; D009414:Nerve Growth Factors; D018342:Receptors, Adrenergic, beta-1; D011976:Receptors, Muscarinic; C482860:UCHL1 protein, human; D014660:Vasoactive Intestinal Peptide; D043222:Ubiquitin Thiolesterase