Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA.
Department of Pharmacology, Case Western Reserve University, Cleveland, OH, USA.
Biol Sex Differ. 2024 Oct 30;15(1):87. doi: 10.1186/s13293-024-00645-9.
Sex as a biological variable is not a common consideration in molecular mechanistic or preclinical studies of retinal diseases. Understanding the sexual dimorphism of adult RPE and retina under physiological conditions is an important first step in improving our understanding of sex-based physio-pathological mechanisms.
Isobaric tags for relative and absolute quantitation (iTRAQ) were used for quantitative proteomics of male and female mouse retina and RPE (10 mice of each sex for each tissue type). Differentially expressed proteins were subjected to Gene Ontology (GO) analysis and Ingenuity Pathway Analysis (IPA).
Differential expression analysis identified 21 differentially expressed proteins in the retina and 58 differentially expressed proteins in the RPE. Ingenuity pathway analysis identified the top canonical pathways differentially activated in the retina to be calcium transport I, nucleotide excision repair, molecular transport and cell death and survival. In the RPE, the top canonical pathways were calcium signaling, dilated cardiomyopathy signaling, actin cytoskeletal signaling and cellular assembly and organization.
These results provide insights into sex differences in the retina and RPE proteome of mice and begin to shed clues into the sexual dimorphism seen in retinal diseases.
在视网膜疾病的分子机制或临床前研究中，性别作为一个生物学变量并不常见。了解成年 RPE 和视网膜在生理条件下的性别二态性是提高我们对基于性别的生理病理机制理解的重要第一步。
采用相对和绝对定量同位素标记技术（iTRAQ）对雄性和雌性小鼠的视网膜和 RPE 进行定量蛋白质组学分析（每种组织类型各有 10 只雌雄小鼠）。对差异表达蛋白进行基因本体（GO）分析和 IPA 分析。
差异表达分析鉴定出视网膜中有 21 个差异表达蛋白，RPE 中有 58 个差异表达蛋白。IPA 分析鉴定出在视网膜中差异激活的主要经典途径为钙转运 I、核苷酸切除修复、分子转运和细胞死亡与存活。在 RPE 中，主要的经典途径是钙信号、扩张型心肌病信号、肌动蛋白细胞骨架信号和细胞组装与组织。
这些结果为我们提供了关于小鼠视网膜和 RPE 蛋白质组中性别差异的见解，并开始揭示出在视网膜疾病中观察到的性别二态性的线索。
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