中南大学湘雅医院计丹团队近日取得一项新成果。经过不懈努力，他们的研究开发出了Dnajb14作为青光眼视网膜神经节细胞存活调节剂的多组学鉴定和验证。该研究于2026年5月26日发表于国际一流学术期刊《遗传学报》杂志上。

课题组研究人员报告了8个稳定的青光眼血浆蛋白靶点，这些靶点是通过结合孟德尔随机化和共定位分析的大规模蛋白质组关联研究确定的。在这些候选蛋白中，该课题组研究人员发现DnaJ热休克蛋白家族成员B14 （DNAJB14）是一个关键的神经保护因子。通过单细胞和大量转录组学，该研究组证明Dnajb14在视网膜神经节细胞（RGCs）中特征性表达，并且其丰度与缺血应激下的铁下垂呈负相关。

此外，他们的研究结果表明，Dnajb14在多种急性和慢性小鼠模型中保持RGC存活和结构和功能完整性。从机制上讲，Dnajb14过表达可明显减轻缺血再灌注引起的视网膜损伤，而靶向敲低可加剧脂质过氧化、线粒体功能障碍和铁下沉。综上所述，他们的发现强调了Dnajb14是通过抑制铁下垂而使RGC存活的关键调节因子，从而使其成为青光眼治疗的有希望的治疗候选者。

研究人员表示，青光眼是不可逆性失明的主要症状，需要确定未报道的治疗靶点。

附：英文原文

Title: Multi-omics identification and verification of Dnajb14 as a modulator of retinal ganglion cell survival in glaucoma through ferroptosis

Author: anonymous

Issue&Volume: 2026/05/26

Abstract: Glaucoma is a leading cause of irreversible blindness and necessitates the identification of unreported therapeutic targets. Here, we report eight stable plasma protein targets for glaucoma, identified through a large-scale proteome-wide association study integrated with Mendelian randomization and colocalization analyses. Among these candidates, we show that the DnaJ heat shock protein family member B14 (DNAJB14) acts as a critical neuroprotective factor. Using single-cell and bulk transcriptomics, we demonstrate that Dnajb14 is characteristically expressed in retinal ganglion cells (RGCs) and that its abundance is inversely correlated with ferroptosis under ischemic stress. Furthermore, our results reveal that Dnajb14 preserve RGC survival and structural and functional integrity in multiple acute and chronic murine models. Mechanistically, Dnajb14 overexpression robustly alleviate ischemia-reperfusion-induced retinal injury, whereas targeted knockdown exacerbate lipid peroxidation, mitochondrial dysfunction, and ferroptosis. Taken together, our findings highlight that Dnajb14 is a key regulator of RGC survival through inhibition of ferroptosis, thereby making it a promising therapeutic candidate for glaucoma treatment.

DOI: 10.1016/j.jgg.2026.05.011

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852726001852