Dixon Angela, Shim Myoung Sup, Nettesheim April, Coyne Aislyn, Su Chien-Chia, Gong Haiyan, Liton Paloma B
Department of Ophthalmology & Pathology, Duke University, Durham, NC, 27705, USA.
Department of Ophthalmology, Boston University School of Medicine, Boston, MA, 02118, USA.
Autophagy Rep. 2024;3(1). doi: 10.1080/27694127.2023.2285214. Epub 2023 Nov 22.
Glaucoma encompasses a spectrum of disorders characterized by the chronic degeneration of retinal ganglion cell (RGC) axons and the progressive loss of RGCs, resulting in visual impairment. In this study, we investigated the effect of autophagy deficiency on two glaucoma hypertensive models, the DBA/2J spontaneous glaucoma model, and the TGFβ2 (transforming growth factor β2) chronic ocular hypertensive model. For this, we used the and DBA/2J- mice, this latter generated in our laboratory via CRISPR/Cas9 technology, which display impaired autophagy. In contrast to littermate WT controls, mice deficient in Atg4B, did not develop glaucomatous elevation of intraocular pressure (IOP). Moreover, autophagy deficiency protected against RGC death and optic nerve atrophy. Collectively, our data supports a pathogenic role of autophagy in the context of ocular hypertension and glaucoma.
青光眼包括一系列以视网膜神经节细胞（RGC）轴突慢性变性和RGC逐渐丧失为特征的疾病，从而导致视力损害。在本研究中，我们调查了自噬缺陷对两种青光眼高血压模型的影响，即DBA/2J自发性青光眼模型和TGFβ2（转化生长因子β2）慢性高眼压模型。为此，我们使用了Atg4B-/-和DBA/2J-Atg4B-/-小鼠，后者是我们实验室通过CRISPR/Cas9技术培育的，表现出自噬受损。与同窝野生型对照相比，Atg4B缺陷小鼠未出现青光眼性眼压（IOP）升高。此外，自噬缺陷可防止RGC死亡和视神经萎缩。总体而言，我们的数据支持自噬在高眼压和青光眼背景下的致病作用。
