Role of epidermal growth factor receptor (EGFR) in corneal remodelling in diabetes
Saeed Akhtar1, Turki Almubrad, Anthony J Bron
1Department of Optometry and Vision Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia. akhtars@ksu.edu.sa
Purpose:
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.
Insights
Epidermal growth factor receptor (EGFR) signaling influences corneal structure in diabetic rats. Inhibiting EGFR normalized collagen and proteoglycan changes, suggesting EGFR
Area of Science:
- Ophthalmology
- Diabetic Complications
- Cell Signaling
Background:
- Diabetic retinopathy is a leading cause of blindness.
- Corneal complications in diabetes can impair vision.
- The role of epidermal growth factor receptor (EGFR) signaling in diabetic corneal remodeling is not fully understood.
Purpose of the Study:
- To investigate the impact of EGFR signaling on collagen fibrils (CFs) and proteoglycans (PGs) organization in the diabetic rat cornea.
- To determine if inhibiting EGFR signaling can prevent diabetes-induced corneal structural changes.
Main Methods:
- Diabetes was induced in Wistar rats using streptozotocin (STZ).
- Rats were treated with AG1478, a selective EGFR tyrosine kinase inhibitor.
- Corneal tissues were analyzed for collagen fibril diameter, area fraction, and proteoglycan distribution using microscopy and specialized software.
Main Results:
- Diabetic rat corneas showed decreased collagen fibril diameter and area fraction, and increased proteoglycan area and area fractions compared to normal corneas.
- AG1478 treatment prevented these alterations in diabetic corneas without affecting normal corneas.
- AG1478-treated diabetic corneas exhibited normalized collagen fibril dimensions and proteoglycan distribution.
Conclusions:
- Diabetes significantly alters corneal stroma organization of collagen fibrils and proteoglycans.
- EGFR signaling inhibition effectively normalized these diabetes-induced corneal abnormalities.
- EGFR plays a critical role in the development of corneal remodeling associated with diabetes.
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