Photoreceptor degeneration is a major cause of blindness and a considerable health burden during aging but effective therapeutic or preventive strategies have not so far become readily available. Here we show in mouse models that signaling through the tyrosine kinase receptor KIT protects photoreceptor cells against both light-induced and inherited retinal degeneration. Upon light damage, photoreceptor cells upregulate Kit ligand (KITL) and activate KIT signaling, which in turn induces nuclear accumulation of the transcription factor NRF2 and stimulates the expression of the antioxidant gene Hmox1. Conversely, a viable Kit mutation promotes light-induced photoreceptor damage, which is reversed by experimental expression of Hmox1. Furthermore, overexpression of KITL from a viral AAV8 vector prevents photoreceptor cell death and partially restores retinal function after light damage or in genetic models of human retinitis pigmentosa. Hence, application of KITL may provide a novel therapeutic avenue for prevention or treatment of retinal degenerative diseases.

中文翻译：

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KIT配体可防止光诱导和遗传性光感受器变性

感光器变性是失明的主要原因，并且在衰老过程中会给健康造成很大负担，但到目前为止，尚无有效的治疗或预防策略。在这里，我们在小鼠模型中显示出通过酪氨酸激酶受体KIT发出的信号可以保护感光细胞免受光诱导和遗传性视网膜变性的侵害。受到光损伤后，感光细胞会上调Kit配体（KITL）并激活KIT信号传导，进而诱导转录因子NRF2的核积累并刺激抗氧化剂基因Hmox1的表达。相反，可行的Kit突变会促进光诱导的感光细胞损伤，这一点可通过Hmox1的实验表达来逆转。此外，从病毒AAV8载体过度表达KITL可防止光感受器细胞死亡，并在光损伤后或在人类视网膜色素变性的遗传模型中部分恢复视网膜功能。因此，KITL的应用可以为预防或治疗视网膜变性疾病提供新的治疗途径。