UCL Inst. of Ophthalmology, London, UK.
Centre for Cell and Gene Therapy, King's College London, London, UK.
Nat Commun. 2022 Apr 20;13(1):2159. doi: 10.1038/s41467-022-29666-x.
Macular degeneration is a leading cause of blindness. Treatments to rescue vision are currently limited. Here, we study how loss of central vision affects lateral feedback to spared areas of the human retina. We identify a cone-driven gain control mechanism that reduces visual function beyond the atrophic area in macular degeneration. This finding provides an insight into the negative effects of geographic atrophy on vision. Therefore, we develop a strategy to restore this feedback mechanism, through activation of laterally projecting cells. This results in improved vision in Cnga3 mice, which lack cone function, as well as a mouse model of geographic atrophy. Our work shows that a loss of lateral gain control contributes to the vision deficit in macular degeneration. Furthermore, in mouse models we show that lateral feedback can be harnessed to improve vision following retinal degeneration.
黄斑变性是失明的主要原因。目前用于挽救视力的治疗方法十分有限。在这里，我们研究了中央视力丧失如何影响人类视网膜未受影响区域的侧向反馈。我们确定了一种由视锥细胞驱动的增益控制机制，该机制降低了黄斑变性萎缩区域之外的视觉功能。这一发现深入了解了地理萎缩对视力的负面影响。因此，我们开发了一种通过激活侧向投射细胞来恢复这种反馈机制的策略。这导致了缺乏视锥细胞功能的 Cnga3 小鼠以及地理萎缩模型小鼠的视力改善。我们的工作表明，侧向增益控制的丧失导致黄斑变性的视力缺陷。此外，在小鼠模型中，我们表明侧向反馈可以在视网膜变性后用于改善视力。
