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A Novel Rat Model for Human Meibomian Gland Dysfunction and Ocular Rosacea
Linxin Zhu1, Daniela Rodrigues-Braz1, Emmanuelle Gélizé1
1Centre de Recherche des Cordeliers, Université de Paris, Sorbonne Université, Inserm, UMRS1138, Team Physiopathology of Ocular Diseases: Therapeutic Innovations, Paris, France.
Purpose:
Ocular rosacea (OR) is a chronic inflammatory and vision-threatening disease of the ocular surface often associated with Meibomian gland dysfunction (MGD). Despite its clinical impact, OR remains underdiagnosed and incurable. The pathogenesis of OR and MGD is poorly understood, partly due to a lack of reliable models. This study aimed to develop a rat model of MGD and OR, and validate its relevance by comparing with the human pathology.
Methods:
Rat upper eyelids were exposed to UVB (300 mJ/cm2/day) for 5 days. Clinical signs, Meibomian gland (MG) morphology, and function were assessed and compared with human OR samples. Transcriptomics and lipidomics were performed to investigate UVB-induced changes.
Results:
UVB caused acute damage to eyelid skin and MGs with increased oxidative stress, mitochondrial dysfunction, apoptosis, inflammation, and elevated lipid production. Whereas inflammation and lipid hyperproduction decreased during the 2-week healing process, MG duct hyperkeratinization and meibocyte stem cell depletion persisted, leading to MGD and corneal epithelial defects. Progressive fibrosis in rat MGs was similar to that observed in human patients with OR, suggesting chronic and irreversible damage to MGs. Transcriptomic analysis showed shared gene regulation patterns between UVB-induced rat MGs and human rosacea and MGD. Lipidomic analysis revealed UVB-induced changes in MG lipid composition.
Conclusions:
This model is a valuable tool for studying the pathophysiology of MGD in OR and evaluating new treatments. The transcriptomic and lipidomic similarities between rat model and human disease provide insights into shared molecular pathways and lipid composition, offering potential biomarkers for diagnosis and therapeutic targets.
Insights
Researchers developed a rat model for ocular rosacea (OR) and Meibomian gland dysfunction (MGD). This model mimics human disease, offering insights into pathophysiology and potential new treatments for this chronic eye condition.
Area of Science:
- Ophthalmology
- Dermatology
- Translational Medicine
Background:
- Ocular rosacea (OR) is a chronic, vision-threatening ocular surface disease linked to Meibomian gland dysfunction (MGD).
- OR and MGD are often underdiagnosed and lack effective cures due to poorly understood pathogenesis.
- Reliable animal models are crucial for advancing research in OR and MGD.
Purpose of the Study:
- To develop and validate a novel rat model of Meibomian gland dysfunction (MGD) and ocular rosacea (OR).
- To compare the induced MGD and OR in rats with human pathology for translational relevance.
Main Methods:
- Rat upper eyelids were exposed to controlled UVB radiation.
- Clinical signs, Meibomian gland morphology/function, transcriptomics, and lipidomics were analyzed.
- Comparisons were made with human ocular rosacea and Meibomian gland dysfunction samples.
Main Results:
- UVB exposure induced acute eyelid and Meibomian gland damage, including oxidative stress and inflammation.
- Persistent Meibomian gland duct hyperkeratinization and stem cell depletion led to MGD and corneal defects.
- The rat model exhibited fibrosis and gene/lipid expression patterns similar to human OR and MGD.
Conclusions:
- The developed rat model is a valuable tool for studying MGD pathophysiology in OR.
- This model aids in evaluating novel therapeutic strategies for ocular rosacea.
- Shared molecular pathways and lipid profiles offer potential biomarkers for diagnosis and treatment targets.
