Sensitized heat shock protein 27 induces retinal ganglion cells apoptosis in rat glaucoma model

Zhao, Wei; Dai, Le; Xi, Xiaoting; Chen, Qian-Bo; An, Meixia; Li, Yan

doi:10.18240/ijo.2020.04.01

Cited by 7 publications

(7 citation statements)

References 43 publications

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“…Our histological findings are also in accordance with those of others [30,34,35]. Microbeads injections induced histological changes between the two limiting layers (OLM-ILM), similar to other retinal injures, such as LPS-induced retinal inflammation [19].…”

Section: Discussionsupporting

confidence: 92%

“…Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide first isolated as a hypothalamic peptide in two biologically active forms (PACAP1- [27][28][29][30][31][32][33][34][35][36][37][38]. It is the most conserved member of the secretin/glucagon/VIP family and it exerts diverse biological actions [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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Retinoprotective Effects of PACAP Eye Drops in Microbead-Induced Glaucoma Model in Rats

Szabó

Patko

Vaczy

et al. 2021

IJMS

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Glaucoma is associated with increased intraocular pressure (IOP), causing the apoptosis of retinal ganglion cells (RGCs) and the loss of their axons leading to blindness. Pituitary adenylate cyclase activating polypeptide (PACAP) is neuroprotective in several neural injuries, including retinopathies. The aim of this study was to investigate the effects of PACAP1-38 eye drops in a model of glaucoma. IOP was elevated bilaterally by injections of microbeads to block the aqueous humor outflow. The control groups received the same volume of saline. Animals were treated with PACAP1-38 (1 µg/drop, 3 × 1 drop/day) or vehicle for 4 weeks starting one day after the injections. Retinal morphology by histology and optical coherence tomography, function by electroretinography, and IOP changes were analyzed. Animals were sacrificed 8 weeks after the injections. Microbeads injections induced a significant increase in the IOP, while PACAP1-38 treatment lowered it to normal levels (~10 mmHg). Significant retinal degeneration and functional impairment were observed in the microbead-injected group without PACAP1-38 treatment. In the microbeads + PACAP1-38 group, the retinal morphology and functionality were close to the normal values. In summary, our results show that PACAP1-38, given in form of eye drops, is neuroprotective in glaucoma, providing the basis for potential future therapeutic administration.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Retinoprotective Effects of PACAP Eye Drops in Microbead-Induced Glaucoma Model in Rats

Szabó

Patko

Vaczy

et al. 2021

IJMS

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“…The ocular hypertension (HP) animal model was generated by condensing 3 episcleral and limbal veins or the episcleral area of the right eye and sham operation group with conjunctiva incision without coagulation (36). Briefly, rats were sedated with 846 mixture (0.1-0.15 per kg; intramuscular injection).…”

Section: Animal Model and Drug Administrationmentioning

confidence: 99%

Acteoside protects retinal ganglion cells from experimental glaucoma by activating the PI3K/AKT signaling pathway via caveolin 1 upregulation

Xi¹,

Chen²,

Ma³

et al. 2022

Ann Transl Med

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Background: Glaucoma is the second leading cause of blindness in the world and is characterized by optic neuropathy and degeneration of retinal ganglion cells (RGCs). Our preliminary research found that acteoside can inhibit autophagy-induced apoptosis of RGCs via the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway. However, it is unclear how acteoside activates the PI3K/AKT signaling pathway to prevents RGCs autophagic apoptosis.Methods: Animal and cell models were used in this study. Hematoxylin-eosin staining revealed pathological histology of retinas. The number of RGCs in retinas was counted using immunofluorescence.Malondialdehyde and superoxide dismutase were determined using enzyme-linked immunosorbent assay kits. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining were used to detect cell apoptosis. The reactive oxygen species was determined by the Flow cytometry. The proteins were determined by Western blot. Results:The results showed that acteoside treatment significantly reduced RGC loss, oxidative stress, and autophagy, thereby preventing glaucoma exacerbation. Acteoside reversed caveolin 1 (Cav1) expression and PI3K/AKT signaling activation, according to Western blot results. Cav1 knockdown also reversed acteoside's effects on RGC loss, PI3K/AKT signaling pathway activation, autophagy and oxidative stress. Notably, 3-methyladenine, a PI3K inhibitor, reversed the effects of acteoside and Cav1 overexpression on RGC loss, oxidative stress, and autophagy.Conclusions: These finding imply that acteoside alleviates RGC loss and oxidative stress by activating of the PI3K/AKT signaling pathway by upregulating Cav1.

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“…The results indicate that HSP27 had an apoptotic effect and induces cell death in the human retina as well as in the surrounding tissue ( Tezel et al, 1998 ). Previous studies revealed that an intraperitoneal, intravitreal, or subcutaneous injection of HSP27 leads to glaucoma-like damage in young rats ( Wax et al, 2008 ; Grotegut et al, 2020 ; Zhao et al, 2020 ). Furthermore, more apoptotic RGCs as well as an increase of apoptotic cells in the optic nerve were noted after HSP27 injection in these rats ( Zhao et al, 2020 ; Grotegut et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

HSP27 induced glaucomatous damage in mice of young and advanced age

Erb,

Reinehr,

Theiss

et al. 2023

Front. Cell. Neurosci.

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IntroductionAge-related diseases such as glaucoma, a leading cause of blindness, are having an upward trend due to an aging society. In glaucoma, some patients display altered antibody profiles and increased antibody titers, for example against heat shock protein 27 (HSP27). An intravitreal injection of HSP27 leads to glaucoma-like damage in rats. We now aimed to investigate if aged mice are more prone to this damage than younger ones.MethodsWe intravitreally injected HSP27 into young (1–2 months) and aged (7–8 months) mice to compare glaucomatous damage. Respective age-matched controls received PBS. Not injected eyes served as naive controls.ResultsOptical coherence tomography 4 weeks after injection showed no changes in retinal thickness in all groups at both ages. Cell counts and RT-qPCR revealed a significant reduction in RGC numbers in HSP27 mice at both ages. Comparing aged and young HSP27 mice, no differences in Rbpms and Pou4f1 (RGCs) expression was detected, while the Tubb3 expression (neuronal cells) was significantly upregulated in aged HSP27 animals. Neither microglia/macrophages nor (resident) microglia counts revealed significant differences in HSP27 mice at both ages. Nevertheless, increased relative Iba1 and Tmem119 expression was detected in young and aged HSP27 mice. Aged HSP27 mice displayed a significantly lower Iba1 expression than young ones, whereas Cd68 levels were upregulated. A larger GFAP+ area and an upregulation of GFAP expression in HSP27 animals of both ages indicated a macrogliosis. Also, elevated Il1b and Nos2 expression levels were observed in young and aged HSP27 mice. However, only Il1b levels were upregulated when comparing 7–8 months to 1–2 months old animals. A larger HSP25+ area was seen in aged HSP27 animals, while Hspb2 expression levels were downregulated in both HSP27 groups. The aged HSP27 group displayed an upregulated Hspb2 expression compared to young mice. Furthermore, a higher optic nerve degeneration score was noted in young and aged HSP27 groups.DiscussionThese findings indicate that an intravitreal injection of HSP27 led to RGC loss accompanied by inflammation. Age-dependent effects (7–8 months vs. 1–2 months) were not very prominent. The results suggest a potential role of extracellular HSP27 in the development of glaucoma.

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Sensitized heat shock protein 27 induces retinal ganglion cells apoptosis in rat glaucoma model

Cited by 7 publications

References 43 publications

Retinoprotective Effects of PACAP Eye Drops in Microbead-Induced Glaucoma Model in Rats

Retinoprotective Effects of PACAP Eye Drops in Microbead-Induced Glaucoma Model in Rats

Acteoside protects retinal ganglion cells from experimental glaucoma by activating the PI3K/AKT signaling pathway via caveolin 1 upregulation

HSP27 induced glaucomatous damage in mice of young and advanced age

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