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<p>Several preclinical data support a main role of Muller glia, a type of retinal glial cells, in sensing hyperglycemia and, subsequently, acquiring a pro-inflammatory polarization during diabetic retinopathy onset and progression. Recently, we reported that stimulation of rat Muller glia cells (rMC1) with high glucose triggers a very early (&lt; 15&#xa0;min) and atypical signaling cascade, regulated by a Ca<sup>2+</sup>-calmodulin/proteasome axis, which induces the nuclear translocation of p65-p50 heterodimer, the principal transcription factor of pro-inflammatory NFkB pathway. In the present study, the repertoire of NF-kB pro-inflammatory genes was early monitored after high-glucose stimulation, in rMC1, as compared to cells stimulated with normal glucose or hyper-osmolar mannitol. The occurrence of an early transcriptional upregulation of most stimulated genes was also verified in rat retina cultures isolated from Sprague-Dawley rats. The overall analysis showed that: <i>(i)</i> high glucose triggers a pro-inflammatory polarization of rMC1 much earlier than previously thought and <i>(ii)</i> this early upregulation recapitulates also in rat retinal culture. Importantly, it has emerged a prominent role played by IL-8 in the early stages of hyperglycemic insult, opening to further studies on its role in primary diabetic retinopathy pathogenesis and envisaging the development of novel potential clinical treatments based on IL-8 blockade.</p>

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High-glucose stimulation triggers early transcription of a panel of proinflammatory mediators in rat Muller glia cells and retina primary explants

  • 期刊论文

  • 发表日期：

    2025年7月4日

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  • Grazia Raffaella Tundo,
  • Maria Grazia Atzori,
  • Alessandra Boccaccini,
  • Dario Cavaterra,
  • Alessio Bocedi,
  • Grazia Graziani,
  • Stefano Marini,
  • Pedro Miguel Lacal,
  • Marika Villa,
  • Flavia Pricci,
  • Monica Varano,
  • Mariacristina Parravano,
  • Diego Sbardella

摘要

Several preclinical data support a main role of Muller glia, a type of retinal glial cells, in sensing hyperglycemia and, subsequently, acquiring a pro-inflammatory polarization during diabetic retinopathy onset and progression. Recently, we reported that stimulation of rat Muller glia cells (rMC1) with high glucose triggers a very early (< 15 min) and atypical signaling cascade, regulated by a Ca2+-calmodulin/proteasome axis, which induces the nuclear translocation of p65-p50 heterodimer, the principal transcription factor of pro-inflammatory NFkB pathway. In the present study, the repertoire of NF-kB pro-inflammatory genes was early monitored after high-glucose stimulation, in rMC1, as compared to cells stimulated with normal glucose or hyper-osmolar mannitol. The occurrence of an early transcriptional upregulation of most stimulated genes was also verified in rat retina cultures isolated from Sprague-Dawley rats. The overall analysis showed that: (i) high glucose triggers a pro-inflammatory polarization of rMC1 much earlier than previously thought and (ii) this early upregulation recapitulates also in rat retinal culture. Importantly, it has emerged a prominent role played by IL-8 in the early stages of hyperglycemic insult, opening to further studies on its role in primary diabetic retinopathy pathogenesis and envisaging the development of novel potential clinical treatments based on IL-8 blockade.