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Hyperglycemia-Reduced Platelet-Derived Growth Factor-BB Expression Impairs Corneal Wound Healing in Diabetic Mice
Yangyang Zhang1,2, Rui Wang1,2,3, Ya Li2
1Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China.
Purpose:
This study investigates the role and primary mechanisms of platelet-derived growth factor-BB (PDGF-BB) in regulating corneal epithelial injury repair and nerve regeneration under diabetic conditions.
Methods:
Type 1 diabetes was induced in C57BL/6 mice via streptozotocin injection. Platelet depletion was achieved using an anti-mouse GPIbα antibody. Platelet levels were quantified in intra- and extravascular compartments of the corneal limbus. Concentrations of growth factors released by activated platelets were measured in human and murine diabetic and nondiabetic samples. Diabetic mice with corneal epithelial wounds received PDGF-BB eye drops alone or combined with ERK1/2 or AKT inhibitors. Platelet-depleted mice were treated with PDGF-BB eye drops, while wild-type C57BL/6 mice received subconjunctival anti-PDGF-BB antibody injections. Human primary corneal limbal epithelial stem cells (HLECs) from diabetic and nondiabetic donors were treated with anti-PDGF-BB antibodies or PDGF-BB small interfering RNA.
Results:
Diabetic individuals exhibited reduced peripheral blood platelet counts and diminished PDGF-BB expression following platelet activation. Both platelet depletion and hyperglycemia impaired corneal epithelial repair and nerve regeneration, correlating with reduced PDGF-BB levels. Inhibiting PDGF-BB signaling significantly delayed corneal epithelial healing and nerve regeneration in wild-type mice. In vitro, PDGF-BB enhanced HLEC migration and proliferation. PDGF-BB promoted corneal epithelial repair and nerve regeneration in diabetic mice via ERK1/2 and AKT pathway activation.
Conclusions:
Hyperglycemia suppresses PDGF-BB expression, impairing corneal epithelial wound healing and nerve regeneration by inhibiting ERK1/2 and AKT signaling. PDGF-BB may represent a potential therapeutic strategy for diabetic keratopathy.
Insights
Diabetic conditions impair corneal healing and nerve repair by reducing platelet-derived growth factor-BB (PDGF-BB). Supplementing PDGF-BB promotes healing via ERK1/2 and AKT pathways, offering a potential therapy for diabetic eye disease.
Area of Science:
- Ophthalmology
- Diabetology
- Regenerative Medicine
Background:
- Diabetic complications often involve impaired wound healing and nerve regeneration.
- Platelet-derived growth factor-BB (PDGF-BB) plays a crucial role in tissue repair.
- The specific mechanisms of PDGF-BB in diabetic corneal healing are not fully understood.
Purpose of the Study:
- To investigate the role of PDGF-BB in diabetic corneal epithelial injury repair and nerve regeneration.
- To elucidate the primary mechanisms by which PDGF-BB influences these processes.
Main Methods:
- Type 1 diabetes was induced in mice; platelet function was modulated using specific antibodies.
- PDGF-BB levels were quantified in human and murine samples.
- Corneal epithelial wounds in diabetic mice were treated with PDGF-BB eye drops, alone or with pathway inhibitors.
- In vitro studies utilized human corneal limbal epithelial stem cells (HLECs).
Main Results:
- Diabetic individuals showed reduced platelet counts and PDGF-BB expression.
- Platelet depletion and hyperglycemia impaired corneal repair and nerve regeneration, linked to lower PDGF-BB.
- PDGF-BB administration enhanced HLEC migration and proliferation.
- PDGF-BB promoted corneal healing and nerve regeneration in diabetic mice via ERK1/2 and AKT pathways.
Conclusions:
- Hyperglycemia suppresses PDGF-BB, hindering corneal healing and nerve regeneration by inhibiting ERK1/2 and AKT signaling.
- PDGF-BB shows potential as a therapeutic agent for diabetic keratopathy.
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