Neurturin-deficient mice develop dry eye and keratoconjunctivitis sicca.

Area of Science:

• Ophthalmology
• Neuroscience
• Immunology

Background:

• Neurturin is a neurotrophic factor crucial for parasympathetic neuron development.
• Neurturin-deficient (NRTN(-/-)) mice exhibit impaired parasympathetic innervation of lacrimal glands.
• Understanding neurturin's role is vital for ocular surface health.

Purpose of the Study:

• To evaluate tear function in NRTN(-/-) mice.
• To assess the ocular surface phenotype in NRTN(-/-) mice.
• To investigate the impact of neurturin deficiency on ocular surface homeostasis.

Main Methods:

• Genomic DNA PCR was used to identify NRTN(-/-) and NRTN(+/+) mice.
• Aqueous tear production, tear clearance, and corneal sensation were measured.
• Corneal permeability, mucin expression, goblet cell density, and inflammatory markers (IL-1beta, MMP-9) were analyzed.

Main Results:

• NRTN(-/-) mice showed reduced tear production, clearance, and sensation, with increased corneal permeability.
• Conjunctival goblet cell density and mucin expression (MUC-4, -5AC) were significantly lower in NRTN(-/-) mice.
• Increased ocular surface inflammation was observed, with elevated IL-1beta, MMP-9, and pro-inflammatory cytokine gene expression.

Conclusions:

• Neurturin deficiency causes ocular surface inflammation and dysfunction, mimicking human dry eye (keratoconjunctivitis sicca).
• This mouse model underscores the importance of the neural network in maintaining ocular surface health.
• Neurturin plays a critical role in the sensory-autonomic regulation of the ocular surface.