<p>Diabetes mellitus, a global epidemic, is a leading cause of blindness due to its detrimental effects on the retina, lens, and cornea. Diabetic keratopathy (DK), a significant ocular complication, severely compromises the corneal epithelium structure, barrier function, and healing capacity, largely driven by hyperglycemia-induced oxidative stress and apoptosis. Current therapeutic strategies for DK are limited and primarily symptomatic, failing to address underlying cellular deficits. This study investigates a novel regenerative approach utilizing a decellularized extracellular matrix (dECM) hydrogel functionalized with the neuroprotective peptide NAP (dECM hydrogel-NAP). Both dECM hydrogels and NAP have demonstrated promising regenerative and protective properties in various tissues, though their combined efficacy for diabetic corneal repair remains unexplored. Using a three-dimensional (3D) organotypic human corneal epithelium model of DK, we evaluated the therapeutic potential of dECM hydrogel-NAP to promote epithelial wound healing, restore barrier function, mitigate apoptotic responses, and support cellular viability under diabetic conditions. Our findings suggest that dECM hydrogel-NAP holds significant promise as a therapeutic strategy for supporting corneal epithelial regeneration in diabetic keratopathy.</p>

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Evaluation of dECM hydrogel-NAP on 3D organotypic human corneal epithelium in diabetic keratopathy model

  • Simona Casarella,
  • Nicoletta Palmeri,
  • Agata Grazia D’Amico,
  • Assunta Virtuoso,
  • Salvatore Saccone,
  • Elisabetta Pricoco,
  • Davide Scollo,
  • Antonio Longo,
  • Michele Papa,
  • Francesca Boccafoschi,
  • Velia D’Agata,
  • Grazia Maugeri

摘要

Diabetes mellitus, a global epidemic, is a leading cause of blindness due to its detrimental effects on the retina, lens, and cornea. Diabetic keratopathy (DK), a significant ocular complication, severely compromises the corneal epithelium structure, barrier function, and healing capacity, largely driven by hyperglycemia-induced oxidative stress and apoptosis. Current therapeutic strategies for DK are limited and primarily symptomatic, failing to address underlying cellular deficits. This study investigates a novel regenerative approach utilizing a decellularized extracellular matrix (dECM) hydrogel functionalized with the neuroprotective peptide NAP (dECM hydrogel-NAP). Both dECM hydrogels and NAP have demonstrated promising regenerative and protective properties in various tissues, though their combined efficacy for diabetic corneal repair remains unexplored. Using a three-dimensional (3D) organotypic human corneal epithelium model of DK, we evaluated the therapeutic potential of dECM hydrogel-NAP to promote epithelial wound healing, restore barrier function, mitigate apoptotic responses, and support cellular viability under diabetic conditions. Our findings suggest that dECM hydrogel-NAP holds significant promise as a therapeutic strategy for supporting corneal epithelial regeneration in diabetic keratopathy.