Corneal endothelial modulation: a factor released by leukocytes induces basic fibroblast growth factor that modulates...

Area of Science:

• Ophthalmology
• Cell Biology
• Biochemistry

Background:

• Corneal endothelial (CE) cells undergo modulation when exposed to corneal endothelium modulation factor (CEMF).
• This modulation involves phenotypic changes in cell shape and collagen synthesis.
• Previous studies identified CEMF's role in CE cell modulation.

Purpose of the Study:

• To investigate the effects of various growth-modulating factors on corneal endothelial modulation.
• To determine the role of basic fibroblast growth factor (bFGF) in CE cell modulation.
• To elucidate the relationship between CEMF and bFGF in CE cell modulation.

Main Methods:

• Assessed cell proliferation via [3H]thymidine incorporation and cell counts.
• Analyzed collagen expression using SDS-PAGE and Northern blot.
• Determined collagen gene transcription rates via nuclear run-off assays.
• Quantified bFGF synthesis using immunoblot and ELISA assays.
• Localized bFGF and its receptors in vivo using immunofluorescence.

Main Results:

• Basic fibroblast growth factor (bFGF) mimicked CEMF-induced modulation, stimulating proliferation, altering cell shape, and shifting collagen synthesis from type IV to types I and V.
• bFGF's effects were augmented by CEMF, which also significantly increased bFGF production in CE cells.
• Transforming growth factor (TGF-beta), epidermal growth factor (EGF), and retinoic acid (RA) did not alter collagen phenotypes in rabbit CE cells.
• Bovine CE cells, unlike rabbit cells, predominantly produced fibrillar collagens, with TGF-beta enhancing type III and inducing type I collagen synthesis.

Conclusions:

• bFGF simultaneously modulates rabbit CE cell proliferation, shape, and collagen expression.
• CEMF induces the synthesis of biologically active bFGF in CE cells.
• bFGF, activated by CEMF, is identified as a key molecule in corneal endothelial modulation and subsequent corneal fibrosis.