Retinal Proteomic Alterations and Combined Transcriptomic-Proteomic Analysis in the Early Stages of Progression of a Mouse Model of X-Linked Retinoschisis
Xiuxiu Jin,
Xiaoli Zhang,
Jingyang Liu,
Weiping Wang,
Meng Liu,
Lin Yang,
Guangming Liu,
Ruiqi Qiu,
Mingzhu Yang,
Shun Yao,
Bo Lei
Affiliations
Xiuxiu Jin
Henan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Xiaoli Zhang
Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
Jingyang Liu
Henan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Weiping Wang
Henan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Meng Liu
Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
Lin Yang
Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
Guangming Liu
Henan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Ruiqi Qiu
Henan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Mingzhu Yang
Henan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Shun Yao
Henan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Bo Lei
Henan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou 450003, China
X-linked retinoschisis (XLRS) is among the most commonly inherited degenerative retinopathies. XLRS is caused by functional impairment of RS1. However, the molecular mechanisms underlying RS1 malfunction remain largely uncharacterized. Here, we performed a data-independent acquisition-mass spectrometry-based proteomic analysis in RS1-null mouse retina with different postal days (Ps), including the onset (P15) and early progression stage (P56). Gene set enrichment analysis showed that type I interferon-mediated signaling was upregulated and photoreceptor proteins responsible for detection of light stimuli were downregulated at P15. Positive regulation of Tor signaling was downregulated and nuclear transcribed mRNA catabolic process nonsense-mediated decay was upregulated at P56. Moreover, the differentially expressed proteins at P15 were enriched in metabolism of RNA and RNA destabilization. A broader subcellular localization distribution and enriched proteins in visual perception and phototransduction were evident at P56. Combined transcriptomic-proteomic analysis revealed that functional impairments, including detection of visible light, visual perception, and visual phototransduction, occurred at P21 and continued until P56. Our work provides insights into the molecular mechanisms underlying the onset and progression of an XLRS mouse model during the early stages, thus enhancing the understanding of the mechanism of XLRS.
