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  3. Hyperglycemia-Reduced Platelet-Derived Growth Factor-BB Expression Impairs Corneal Wound Healing in Diabetic Mice

Hyperglycemia-Reduced Platelet-Derived Growth Factor-BB Expression Impairs Corneal Wound Healing in Diabetic Mice

  • Invest Ophthalmol Vis Sci. 2025 Aug 1;66(11):61. doi: 10.1167/iovs.66.11.61.
Yangyang Zhang 1 2,  Rui Wang 1 2 3,  Ya Li 2,  Wei Zhu 4,  Yanling Liu 2 3,  Zhenzhen Zhang 1 2,  Xia Qi 2,  Huabo Chen 1,  Qingjun Zhou 1 2,  Lixin Xie 1 2
Affiliations

Affiliations

  • 1 Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China.
  • 2 State Key Laboratory Cultivation Base, Shandong Key Laboratory of Eye Diseases, Qingdao, China.
  • 3 School of Ophthalmology, Shandong First Medical University, Jinan, China.
  • 4 Affiliated Hospital of Qingdao University, Qingdao, China.
PMID: 40856651 DOI: 10.1167/iovs.66.11.61
Abstract

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.

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