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PEDF Gene Deletion Disrupts Corneal Innervation and Ocular Surface Function.
Zhenying Shang1, Chenxi Li1, Xuemei Liu1
1Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
Investigative Ophthalmology & Visual Science
|June 16, 2021
Summary
Pigment epithelium-derived factor (PEDF) is crucial for maintaining corneal structure and function. Its absence leads to reduced innervation, sensitivity, and increased injury, highlighting PEDF
Area of Science:
- Ophthalmology
- Molecular Biology
- Neuroscience
Background:
- The cornea's integrity relies on innervation from the trigeminal ganglion (TG) and support from lacrimal (LG) and meibomian glands (MG).
- Pigment epithelium-derived factor (PEDF) plays a role in ocular surface homeostasis, but its specific impact on corneal structure and function is not fully understood.
Purpose of the Study:
- To investigate the effects of pigment epithelium-derived factor (PEDF) gene deletion on corneal structure, innervation, sensitivity, and tear production.
- To explore the molecular mechanisms underlying PEDF's role in maintaining corneal health.
Main Methods:
- Utilized PEDF hemizygous and homozygous knockout mice.
- Assessed corneal innervation via beta tubulin staining.
- Measured corneal sensitivity using a Cochet-Bonnet esthesiometer.
- Quantified tear production using the phenol red cotton thread wetting method.
- Analyzed mRNA expression of trophic factors and putative PEDF receptors in the cornea and supporting glands (TG, LG, MG).
Main Results:
- PEDF deficiency resulted in reduced corneal innervation and sensitivity, increased corneal surface injury, and elevated tear production.
- Corneal stroma thinned, and stromal cells were lost in PEDF-deficient mice.
- PEDF deletion altered the expression of key trophic factors (NGF, BDNF, GDNF, NT-3, EGF) and putative PEDF receptors in the cornea and supporting glands.
- Significantly altered ERK1/2 and Akt signaling pathways were observed in the TG and cornea.
Conclusions:
- PEDF is essential for maintaining corneal structure and function.
- PEDF acts as a key coordinator of molecular mechanisms regulating corneal health.
- The findings suggest therapeutic potential for PEDF in treating ocular surface diseases.
