Neurodegeneration and cellular stress in the retina and optic nerve in rat cerebral ischemia and hypoperfusion models

Kalesnykas, Giedrius; Tuulos, Timo; Uusitalo, Hannu; Jolkkonen, Jukka

doi:10.1016/j.neuroscience.2008.06.038

Cited by 71 publications

(70 citation statements)

References 42 publications

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“…In this study, we demonstrate that stabilized HIF-1a is also present in normal human retina. Our findings in rats confirm this, and they are in line with earlier reports showing the presence of nuclear HIF-1a protein in non-diabetic rat retina (Poulaki et al 2002;Calvert et al 2004;Kalesnykas et al 2008). The nuclear staining pattern and the immunoblotting data of nuclear extracts indicate that stabilized HIF-1a was located in the nuclei.…”

Section: Discussionsupporting

confidence: 93%

Active HIF-1 in the Normal Human Retina

Hughes

Groot

Groep

et al. 2009

J Histochem Cytochem.

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S U M M A R Y A unique feature of the retina is the presence of photoreceptors, which require an enormous amount of oxygen for the conversion of light to an electrical signal. Hypoxia-inducible factor-1 alpha (HIF-1a) is a transcription factor that is the master regulator of cellular adaptation to low oxygen tension. Only in hypoxic conditions is HIF-1a protein stabilized and translocated to the nucleus, where it induces transcription of target genes involved in oxygen delivery and energy metabolism. We hypothesized that HIF-1a is constitutively stabilized and active in the normal human retina. We investigated the cellular distribution of HIF-1a and the expression of its downstream targets, vascular endothelial growth factor (VEGF), glucose transporter 1 (GLUT-1), and carbonic anhydrase IX (CAIX), by immunohistochemistry and immunoblotting in the retina of normal rats and human donor eyes. Both human and rat retinas displayed prominent staining of HIF-1a in nuclei of most cell types in inner and outer nuclear layers and the ganglion cell layer, a cellular distribution pattern which was confirmed in human retina by immunoblotting of nuclear extracts. A negative correlation was found between HIF-1a protein levels and postmortem times. In human retina, staining of VEGF, GLUT-1, and CAIX was found. Our observations indicate that active HIF-1 signaling occurs constitutively in the normal human and rat retina, suggesting that HIF-1 has a physiological role in the retina. (J Histochem Cytochem 58:247-254, 2010)

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Section: Discussionsupporting

confidence: 93%

Active HIF-1 in the Normal Human Retina

Hughes

Groot

Groep

et al. 2009

J Histochem Cytochem.

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“…In general, HspB1 immunoreactivity is low in the rat retina; however, results as to where HspB1 is present have varied. HspB1 has been detected in the rat ganglion cell layer [14][15][16], and HspB1 has been detected in RGCs of the adult pig [13]. In rats, HspB1 immunoreactivity also occurs in the inner plexiform layer, inner nuclear layer, outer limiting membrane and adjacent photoreceptor nuclei, in the inner segments of photoreceptors, and at the tips of photoreceptor outer segments, possibly including processes of retinal pigment epithelial cells.…”

Section: Constitutive Expression Of Hspb1mentioning

confidence: 99%

“…HspB1 was also present in retinal blood vessels [14]. In addition to the ganglion cell layer, HspB1 was also expressed highly in photoreceptor outer segments and in retinal pigment epithelium cells [15] and in the nerve fiber layer [16]. However, one study reported basal expression observed only in cells of the choroidal and retinal vasculature [17].…”

Section: Constitutive Expression Of Hspb1mentioning

confidence: 99%

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HspB1 (Hsp 27) Expression and Neuroprotection in the Retina

2010

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Heat shock proteins (Hsps) are highly conserved proteins that are induced in response to various physiological and environmental stressors. HspB1 (Hsp27) is a prominent member of the small Hsps family and is strongly induced during the stress response. Notably, HspB1 has powerful neuroprotective effects, increasing the survival of cells subjected to cytotoxic stimuli. This is especially relevant to the study of the retina, where cells are subject to death due to retinal disease and injury. While HspB1 shows constitutive expression in some areas of the mammalian retina, of particular interest is the upregulation of the protein in response to ischemia and oxidative stress, traumatic nerve injury, and elevated intraocular pressure and glaucoma. Several mechanisms have been proposed to account for the cytoprotective actions of HspB1, including its role as a molecular chaperone, a stabilizer of the cytoskeleton, and a regulator of apoptosis. This review will focus on the role of HspB1 in the retina, emphasizing effects on retinal ganglion cells, by analyzing the expression, induction by stressors, and mechanisms of its neuroprotective function. Finally, the potential of HspB1 as a clinical therapeutic will be examined.

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“…17 HSP27 was markedly expressed in retinal glial cells including in Müller cell processes in the ONL. 18,19 The protective effect of HSP27 on GCs was also observed in a retinal ischemia rat model when HSP27 was applied to the vitreous through electroinjection. 20 Furthermore, an HSP27 antibody administered to retinal cells in vivo and ex vivo revealed DNA fragmentation and caspase activation and facilitated cell apoptosis.…”

mentioning

confidence: 92%

Suppression of HSP27 Restores Retinal Function and Protects Photoreceptors From Apoptosis in a Light-Induced Retinal Degeneration Animal Model

Chien

Huang

Tien

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. We used a light-induced retinal degeneration animal model to investigate possible roles of heat shock protein 27 (HSP27) in retinal/photoreceptor protection.METHODS. Sprague-Dawley rats were used for the light-induced retinal degeneration animal model. The histology of eye sections was observed for morphologic changes in the retina. Cell apoptosis was examined in each group using the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and electroretinography was used to evaluate retinal function. Protein and mRNA expression levels of different retinal cell markers were also detected through immunofluorescence staining, Western blotting, and real-time PCR.RESULTS. The thickness of the outer nuclear layer significantly decreased after 7-day light exposure. Moreover, we injected a viral vector for silencing HSP27 expression into the eyes and observed that photoreceptors were better preserved in the HSP27-suppressed (sHSP27) retina 2 weeks after injection. HSP27 suppression also reduced retinal cell apoptosis caused by light exposure. In addition, the loss of retinal function caused by light exposure was reversed on suppressing HSP27 expression. We subsequently found that the expression of the Rho gene and immunofluorescence staining of rhodopsin and arrestin (cell markers for photoreceptors) increased in sHSP27-treated retinas. HSP27 suppression did not affect the survival of ganglion and amacrine cells. CONCLUSIONS.Retinal cell apoptosis and functional loss were observed after 7-day light exposure. However, in the following 2 weeks after light exposure, HSP27 suppression may initiate a protective effect for retinal cells, particularly photoreceptors, from light-induced retinal degeneration.

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Neurodegeneration and cellular stress in the retina and optic nerve in rat cerebral ischemia and hypoperfusion models

Cited by 71 publications

References 42 publications

Active HIF-1 in the Normal Human Retina

Active HIF-1 in the Normal Human Retina

HspB1 (Hsp 27) Expression and Neuroprotection in the Retina

Suppression of HSP27 Restores Retinal Function and Protects Photoreceptors From Apoptosis in a Light-Induced Retinal Degeneration Animal Model

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