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<p>Inflammation is a key driver of atrophic Age-Related Macular Degeneration (aAMD), and also plays a role in Inherited Retinal Degenerations (IRDs), two major causes of irreversible visual loss. We previously demonstrated that the C-C chemokine receptor type 1 (CCR1) is upregulated in monocytes from AMD patients, and that it mediates the recruitment of neurotoxic macrophages and activates Müller glial cells in rodent model of photic retinal injury. Here we report that CCR1 is expressed in Müller glia in eyes affected by AMD and that variants in <i>CCR1</i> are potentially associated with the rate of macular atrophy progression in AMD. We also show that <i>Ccr1</i> deletion is associated with reduced inflammation, and with rescue of photoreceptor integrity and function in Crb1<sup>rd8/rd8</sup> mice and in Pde6b<sup>rd10</sup> mice, two models of genetically-driven retinal degeneration. Finally, we demonstrate that treatment with small molecule CCR1 antagonists delayed photoreceptor loss in Pde6b<sup>rd10</sup> mice. These data suggest that CCR1 is a mediator of retinal inflammation and injury in different forms of retinal degeneration, and that CCR1 may serve as a novel therapeutic target for atrophic AMD and IRDs.</p>

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CCR1 signaling as a common injury pathway in retinal degeneration

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月17日

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  • Sarah Elbaz-Hayoun,
  • Lian Omari,
  • Shlomit Jaskoll,
  • Adi Kramer,
  • Batya Rinsky,
  • Maya Eiger-Moscovich,
  • Ying Song,
  • Joshua L. Dunaief,
  • Sandro De Zanet,
  • Stefanos Apostolopoulos,
  • Carlos Ciller,
  • Itay Chowers

摘要

Inflammation is a key driver of atrophic Age-Related Macular Degeneration (aAMD), and also plays a role in Inherited Retinal Degenerations (IRDs), two major causes of irreversible visual loss. We previously demonstrated that the C-C chemokine receptor type 1 (CCR1) is upregulated in monocytes from AMD patients, and that it mediates the recruitment of neurotoxic macrophages and activates Müller glial cells in rodent model of photic retinal injury. Here we report that CCR1 is expressed in Müller glia in eyes affected by AMD and that variants in CCR1 are potentially associated with the rate of macular atrophy progression in AMD. We also show that Ccr1 deletion is associated with reduced inflammation, and with rescue of photoreceptor integrity and function in Crb1rd8/rd8 mice and in Pde6brd10 mice, two models of genetically-driven retinal degeneration. Finally, we demonstrate that treatment with small molecule CCR1 antagonists delayed photoreceptor loss in Pde6brd10 mice. These data suggest that CCR1 is a mediator of retinal inflammation and injury in different forms of retinal degeneration, and that CCR1 may serve as a novel therapeutic target for atrophic AMD and IRDs.