Mucin deficiency causes functional and structural changes of the ocular surface

Area of Science:

• Ophthalmology
• Mucinology
• Immunology

Background:

• Mucin 5AC (MUC5AC) is the primary gel-forming mucin in the ocular system, but its specific role in ocular surface health is not fully understood.
• Ocular surface integrity and tear film stability are crucial for maintaining vision and comfort.

Purpose of the Study:

• To investigate the physiological function of MUC5AC in the ocular system using a MUC5AC-deficient mouse model.
• To evaluate the impact of MUC5AC absence on tear film dynamics, corneal health, and ocular surface characteristics.

Main Methods:

• Generation and characterization of a Muc5ac knockout (KO) mouse model.
• Physiological measurements including tear break-up time (TBUT), corneal fluorescein staining, and tear volume assessment.
• Analysis of Muc5b expression in KO mice and comparison with wild-type (WT) controls.

Main Results:

• Muc5ac KO mice showed significantly lower tear break-up time (TBUT) and higher corneal fluorescein staining scores compared to WT mice.
• Tear volume remained unchanged between KO and WT mice, indicating a qualitative rather than quantitative change in tear fluid.
• Increased Muc5b expression was observed in the conjunctiva of KO mice, and some KO mice developed corneal opacification.

Conclusions:

• The absence of MUC5AC significantly impacts the quality of the tear film, leading to clinical features consistent with dry eye disease.
• Muc5ac knockout mice represent a valuable preclinical model for investigating the pathophysiology of dry eye disease and the role of mucins in ocular surface homeostasis.