Role of epidermal growth factor receptor (EGFR) in corneal remodelling in diabetes.
OBJECTIVE
This study examined the role of epidermal growth factor receptor (EGFR) signalling on the organization and remodelling of collagen fibrils (CFs) and proteoglycans (PGs) in the stroma of diabetic rat cornea.


METHODS
Diabetes was induced in female Wistar rats (n = 5) by streptozotocin (STZ) injection (55 mg/kg). Treatment with a selective inhibitor of EGFR tyrosine kinase, AG1478, was started on the same day as the induction of diabetes and administered every other day for 4 weeks. Corneas were fixed in 4% paraformaldehyde at 4 degrees to allow for analysis of CF diameters and in 2.5% glutaraldehyde in sodium acetate buffer containing cuprolinic blue to enable the study of PG distribution. AnalySIS soft imaging software was used to analyse CFs and PGs.


RESULTS
Epithelial thickness, and median diameter and area fraction of CF in corneal stroma were decreased in diabetic rat cornea compared with normal cornea (p < 0.001), whereas the median PG area and area fractions were significantly increased (p < 0.001). Treatment with AG1478, although it had no action on normal cornea, prevented these diameter and area fraction changes in CFs and PGs. The cornea of AG1478-treated diabetic rats showed a slight increase in CF diameter and area fraction and a decreased number density.


CONCLUSIONS
These data show that the distribution of corneal stroma CFs and PGs was altered after 4 weeks of diabetes and that, furthermore, treatment with an EGFR signalling inhibitor normalized these abnormalities. The data suggest that EGFR plays an important role in the development of diabetes-induced corneal remodelling.
Akhtar
Saeed
S
Department of Optometry and Vision Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia. akhtars@ksu.edu.sa
Almubrad
Turki
T
Bron
Anthony J
AJ
Yousif
Mariam H M
MH
Benter
Ibrahim F
IF
Akhtar
Saghir
S
D000818:Animals; D003094:Collagen / Q000378:metabolism / Q000648:ultrastructure; D003315:Cornea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003319:Corneal Stroma / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D008854:Microscopy, Electron; D011509:Proteoglycans / Q000378:metabolism / Q000648:ultrastructure; D011799:Quinazolines; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014018:Tissue Distribution; D020032:Tyrphostins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011509:Proteoglycans; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D003094:Collagen; D066246:ErbB Receptors