Caveolin-1 protects retinal ganglion cells in glaucoma by reducing TLR4 and activating the Akt/PTEN signaling pathway

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2024-08-22 DOI:10.1016/j.prp.2024.155552

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引用次数: 0

Abstract

Glaucoma is a degenerative disease characterized by retinal ganglion cell (RGC) death and visual impairment caused by elevated intraocular pressure (IOP). Elevated IOP can activate microglia, which participate in ganglion cell injury. Based on the study of caveolin-1 (Cav-1) in glaucoma, we aimed to explore the effect and mechanism of Cav-1 on RGC apoptosis in mice with acute ocular hypertension (AOH). AOH mice were established, and Cav-1 was intravitreally injected. Retinal microglia and RGCs were isolated from neonatal mice. TUNEL staining, hematoxylin-eosin staining, immunohistochemistry, flow cytometry, PCR and western blotting were used to observe the effect of Cav-1 on RGCs and mouse retinas. The thickness of the whole retina and the inner retinal sublayer decreased significantly, retinal cell apoptosis increased after AOH injury, and Cav-1 treatment reversed the effect of AOH injury. In addition, Cav-1 treatment promoted the conversion of proinflammatory M1 microglia to anti-inflammatory M2 microglia. Microglia and RGCs were isolated from neonatal mice. Cav-1 protects RGCs from OGD/R-induced injury by changing the polarization status of retinal microglia in vitro. Further studies revealed that Cav-1 activated the Akt/PTEN signaling pathway and inhibited TLR4. Our study provides evidence that Cav-1 may be a promising therapeutic target for glaucoma.

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Caveolin-1 通过减少 TLR4 和激活 Akt/PTEN 信号通路保护青光眼视网膜神经节细胞

青光眼是一种退行性疾病，其特点是眼压升高导致视网膜神经节细胞（RGC）死亡和视力受损。眼压升高可激活小胶质细胞，而小胶质细胞参与神经节细胞损伤。基于洞穴素-1（Cav-1）在青光眼中的研究，我们旨在探讨Cav-1对急性眼压升高（AOH）小鼠RGC凋亡的影响和机制。我们建立了 AOH 小鼠，并在玻璃体内注射了 Cav-1。从新生小鼠体内分离视网膜小胶质细胞和RGC。采用TUNEL染色、苏木精-伊红染色、免疫组化、流式细胞术、PCR和Western印迹法观察Cav-1对RGCs和小鼠视网膜的影响。AOH损伤后，整个视网膜和视网膜内亚层的厚度明显下降，视网膜细胞凋亡增加，而Cav-1能逆转AOH损伤的影响。此外，Cav-1还能促进促炎性M1小胶质细胞向抗炎性M2小胶质细胞转化。从新生小鼠体内分离出小胶质细胞和RGCs。Cav-1通过改变体外视网膜小胶质细胞的极化状态，保护RGC免受OGD/R诱导的损伤。进一步的研究发现，Cav-1 能激活 Akt/PTEN 信号通路并抑制 TLR4。我们的研究提供了证据，证明Cav-1可能是治疗青光眼的一个有前景的靶点。

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.