Comparative Analysis of Age-Associated Changes in Meibum Composition, Distribution, and Function in Mice With Altered...

Area of Science:

• Ophthalmology
• Biochemistry
• Genetics

Background:

• Meibomian gland (MG) dysfunction is a primary cause of dry eye disease (DED).
• Hyaluronan (HA) synthase 1 and 3 (Has1 and Has3) are key enzymes in HA production.
• Mice lacking Has1 and Has3 are known to resist MG atrophy.

Purpose of the Study:

• To investigate the impact of lacking hyaluronan synthase 1 and 3 on meibum composition and distribution with aging.
• To determine if Has1-/-; Has3-/- mice are protected from developing dry eye disease.

Main Methods:

• Lipid composition and meibum distribution were analyzed in wild-type (wt) and Has1-/-; Has3-/- mice.
• Expression of meibum biosynthetic enzymes was assessed via real-time PCR.
• Tear film stability and DED symptoms were evaluated using a benzalkonium chloride model and aged mice.

Main Results:

• Has1-/-; Has3-/- mice exhibited sustained meibum production and composition with aging compared to wt mice.
• These mice showed significantly fewer age-related changes in meibum lipids.
• Has1-/-; Has3-/- mice displayed reduced corneal opacity and epithelial erosions, indicating protection from DED.

Conclusions:

• Overexpression of an HA-rich matrix prevents MG atrophy and promotes healthy meibum production.
• This supports tear film stability and protects the ocular surface from age-related DED.
• Targeting hyaluronan synthesis may offer a therapeutic strategy for DED.