Specific Inner Retinal Layer Cell Damage in an Autoimmune Glaucoma Model Is Induced by GDNF With or Without HSP27

Casola, Christina; Reinehr, Sabrina; Kuehn, Sandra; Stute, Gesa; Spiess, Bernhard M.; Dick, H. Burkhard; Joachim, Stephanie C.

doi:10.1167/iovs.15-18999r2

Cited by 28 publications

(29 citation statements)

References 44 publications

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“…4′,6 diamidino-2-phenylindole (DAPI; Serva Electrophoresis, Heidelberg, Germany) helped with visualizing the cell nuclei. For each staining, a negative control was performed by using the secondary antibody only [ 97 , 98 ]. In order to provide equal conditions for comparable outcomes, for each staining, antibodies with the same batch numbers were used and the same staining processes were executed.…”

Section: Methodsmentioning

confidence: 99%

Synapse and Receptor Alterations in Two Different S100B-Induced Glaucoma-Like Models

Benning¹,

Reinehr²,

Grotegut³

et al. 2020

IJMS

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Glaucoma is identified by an irreversible retinal ganglion cell (RGC) loss and optic nerve damage. Over the past few years, the immune system gained importance in its genesis. In a glaucoma-like animal model with intraocular S100B injection, RGC death occurs at 14 days. In an experimental autoimmune glaucoma model with systemic S100B immunization, a loss of RGCs is accompanied by a decreased synaptic signal at 28 days. Here, we aimed to study synaptic alterations in these two models. In one group, rats received a systemic S100B immunization (n = 7/group), while in the other group, S100B was injected intraocularly (n = 6–7/group). Both groups were compared to appropriate controls and investigated after 14 days. While inhibitory post-synapses remained unchanged in both models, excitatory post-synapses degenerated in animals with intraocular S100B injection (p = 0.03). Excitatory pre-synapses tendentially increased in animals with systemic S100B immunization (p = 0.08) and significantly decreased in intraocular ones (p = 0.04). Significantly more n-methyl-d-aspartate (NMDA) receptors (both p ≤ 0.04) as well as gamma-aminobutyric acid (GABA) receptors (both p < 0.03) were observed in S100B animals in both models. We assume that an upregulation of these receptors causes the interacting synapse types to degenerate. Heightened levels of excitatory pre-synapses could be explained by remodeling followed by degeneration.

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Section: Methodsmentioning

confidence: 99%

Synapse and Receptor Alterations in Two Different S100B-Induced Glaucoma-Like Models

Benning¹,

Reinehr²,

Grotegut³

et al. 2020

IJMS

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“…Laser lines and emission filters were optimized using the Zeiss LSM Image Browser software. Staining signal areas were analyzed using ImageJ software (ImageJ 1.47t, National Institutes of Health, Bethesda, MD, USA) as described previously5281. Briefly, photos were transferred into greyscale pictures.…”

Section: Methodsmentioning

confidence: 99%

Ischemic injury leads to extracellular matrix alterations in retina and optic nerve

Reinhard

Renner

Wiemann

et al. 2017

Sci Rep

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Retinal ischemia occurs in a variety of eye diseases. Restrained blood flow induces retinal damage, which leads to progressive optic nerve degeneration and vision loss. Previous studies indicate that extracellular matrix (ECM) constituents play an important role in complex tissues, such as retina and optic nerve. They have great impact on de- and regeneration processes and represent major candidates of central nervous system glial scar formation. Nevertheless, the importance of the ECM during ischemic retina and optic nerve neurodegeneration is not fully understood yet. In this study, we analyzed remodeling of the extracellular glycoproteins fibronectin, laminin, tenascin-C and tenascin-R and the chondroitin sulfate proteoglycans (CSPGs) aggrecan, brevican and phosphacan/RPTPβ/ζ in retinae and optic nerves of an ischemia/reperfusion rat model via quantitative real-time PCR, immunohistochemistry and Western blot. A variety of ECM constituents were dysregulated in the retina and optic nerve after ischemia. Regarding fibronectin, significantly elevated mRNA and protein levels were observed in the retina following ischemia, while laminin and tenascin-C showed enhanced immunoreactivity in the optic nerve after ischemia. Interestingly, CSPGs displayed significantly increased expression levels in the optic nerve. Our study demonstrates a dynamic expression of ECM molecules following retinal ischemia, which strengthens their regulatory role during neurodegeneration.

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“…In addition, in DBA/2J mice more microglia were noted after three months of age. The immunization with HSP27 in combination with glial cell line-derived neurotrophic factor (GDNF) also increased the number of microglia, but did not activate them after 4 weeks [63]. However, microglia response could occur at a different point in time after intravitreal HSP27 injection.…”

Section: No Glia Cell Responsementioning

confidence: 99%

“…For western blot analysis, retinas (n = 5-6/group) were prepared as previously described [63]. Briefly, for protein isolation, frozen retinas were mechanically homogenized with homogenizer pestle (neoLab, Heidelberg, Germany) in 150 µL lysis buffer (RIPA buffer; Cell Signaling Technology, Danvers, MA, USA) containing protease inhibitor (Sigma-Aldrich).…”

Section: Western Blot Analysismentioning

confidence: 99%

Destructive Effect of Intravitreal Heat Shock Protein 27 Application on Retinal Ganglion Cells and Neurofilament

Grotegut¹,

Kuehn²,

Dick³

et al. 2020

IJMS

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Heat shock protein 27 (HSP27) is commonly involved in cellular stress. Increased levels of HSP27 as well as autoantibodies against this protein were previously detected in glaucoma patients. Moreover, systemic immunization with HSP27 induced glaucoma-like damage in rodents. Now, for the first time, the direct effects of an intravitreal HSP27 application were investigated. For this reason, HSP27 or phosphate buffered saline (PBS, controls) was applied intravitreally in rats (n = 12/group). The intraocular pressure (IOP) as well as the electroretinogram recordings were comparable in HSP27 and control eyes 21 days after the injection. However, significantly fewer retinal ganglion cells (RGCs) and amacrine cells were observed in the HSP27 group via immunohistochemistry and western blot analysis. The number of bipolar cells, on the other hand, was similar in both groups. Interestingly, a stronger neurofilament degeneration was observed in HSP27 optic nerves, while no differences were noted regarding the myelination state. In summary, intravitreal HSP27 injection led to an IOP-independent glaucoma-like damage. A degeneration of RGCs as well as their axons and amacrine cells was noted. This suggests that high levels of extracellular HSP27 could have a direct damaging effect on RGCs.

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Specific Inner Retinal Layer Cell Damage in an Autoimmune Glaucoma Model Is Induced by GDNF With or Without HSP27

Cited by 28 publications

References 44 publications

Synapse and Receptor Alterations in Two Different S100B-Induced Glaucoma-Like Models

Synapse and Receptor Alterations in Two Different S100B-Induced Glaucoma-Like Models

Ischemic injury leads to extracellular matrix alterations in retina and optic nerve

Destructive Effect of Intravitreal Heat Shock Protein 27 Application on Retinal Ganglion Cells and Neurofilament

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