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Laura Motterle, MD; Yolanda Diebold, PhD; Amalia Enríquez de Salamanca, PhD; Victoria Saez, BS; Carmen Garcia-Vazquez, BS; Michael E. Stern, PhD; Margarita Calonge, MD; Andrea Leonardi, MD

Arch Ophthalmol. 2006;124:462-468.

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; ₁-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, M₁muscarinic receptor, nerve growth factor, and protein gene product 9.5 expression were decreased, whereas M₂ and M₃ muscarinic receptors and ₁-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 ₁-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.

Author Affiliations: Department of Neuroscience, Ophthalmology Unit, University of Padova, Padova, Italy (Drs Motterle and Leonardi); Instituto Universitario de Oftalmobiologia Aplicada, University of Valladolid, Valladolid, Spain (Drs Diebold, Enríquez de Salamanca, and Calonge and Mss Saez and Garcia-Vazquez); and Allergan Inc, Irvine, Calif (Dr Stern).

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