PACAP through EGFR transactivation preserves human corneal endothelial integrity

Area of Science:

• Ophthalmology
• Cell Biology
• Regenerative Medicine

Background:

• The corneal endothelium, a single layer of hexagonal cells, maintains corneal clarity by regulating hydration.
• Loss of corneal endothelial cells due to trauma or disease impairs tissue function.
• Human corneal endothelial cells (HCECs) offer potential for regenerative medicine, but their survival needs enhancement.

Purpose of the Study:

• To elucidate the molecular mechanisms by which pituitary adenylate cyclase-activating polypeptide (PACAP) protects human corneal endothelial cells (HCECs).
• To investigate the expression of PACAP and its receptor (PAC1R) in the human corneal endothelium.
• To determine the signaling pathways activated by PACAP in HCECs.

Main Methods:

• Demonstration of PACAP and PAC1R expression in human corneal endothelium.
• Analysis of PACAP's selective binding to PAC1R.
• Investigation of epidermal growth factor receptor (EGFR) phosphorylation and MAPK/ERK1/2 pathway activation following PACAP treatment.

Main Results:

• PACAP and its receptor (PAC1R) are expressed in the human corneal endothelium.
• PACAP selectively binds to PAC1R, initiating downstream signaling.
• PACAP induces EGFR phosphorylation and activates the MAPK/ERK1/2 pathway in HCECs.

Conclusions:

• PACAP acts as a trophic factor, maintaining human corneal endothelial integrity via EGFR transactivation.
• PACAP, alongside growth factors like EGF and FGF, may cooperate to support corneal endothelial barrier function.
• These findings suggest PACAP as a potential therapeutic agent for corneal endothelial disorders.