scholarly journals Role of Heat Shock Proteins in Glaucoma

2019 ◽  
Vol 20 (20) ◽  
pp. 5160 ◽  
Author(s):  
Teresa Tsai ◽  
Pia Grotegut ◽  
Sabrina Reinehr ◽  
Stephanie C. Joachim
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Retinal Ganglion Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ganglion Cells ◽  
Nerve Degeneration ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Shock Proteins

Glaucoma, one of the most common causes of blindness worldwide, is a multifactorial neurodegenerative disease characterized by damage of retinal ganglion cells and optic nerve degeneration. However, the exact mechanism leading to glaucoma is still not understood. Evidences suggest an immunological involvement in the pathogenesis. Among other immune responses, altered autoantibody patterns were found in glaucoma patients. Especially elevated antibody levels against heat shock proteins (HSPs), like HSP27 or HSP60, were identified. In an animal model, an immunization with these HSPs induced a pressure-independent retinal ganglion cell degeneration and axon loss, hence mimicking glaucoma-like damage. In addition, development of autoreactive antibodies, as well as a glia and T-cell activation, were described in these animals. Recently, we noted that intravitreal HSP27 injection likewise led to a degeneration of retinal ganglion cells and their axons. Therefore, HSP27 might have a direct damaging effect on retinal cells, and might play a key role in glaucoma.

The Role of Heat Shock Proteins in the Mechanisms of Neurodegeneration and Neuroprotection in Primary Glaucoma: Literature Review

2021 ◽  
pp. 122-131
Author(s):  
N. S. Lutsenko ◽  
T. V. Nedilka
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Neurodegenerative Diseases ◽  
Retinal Ganglion Cells ◽  
Defense Mechanism ◽  
Ganglion Cells ◽  
The Body ◽  
Retinal Ganglion ◽  
Shock Proteins

Heat shock proteins (HSP) are important components of the defense mechanism that increases the survival of body cells in adverse conditions due to antiapoptotic and cytoprotective effects. Since their discovery, numerous studies and experimental models have proved the role of HSPs as a key link in the processes of both repair and coagulation of proteins, as well as in the protection of cells from oxidative stress. The potential for pharmacological induction of HSPs in the human body makes them an attractive therapeutic target for many neurodegenerative diseases. This review examines the role of HSPs, especially fraction 70, in the mechanisms of neuroprotection of retinal ganglion cells in primary open-angle glaucoma being one of the common neurodegenerative diseases that can lead to complete loss of visual functions. A number of studies have shown the protective effect of HSP70 on retinal ganglion cells in animals with artificially induced glaucoma. But in the course of experiments on animal models, it was also proved that direct immunization with HSP through intravitreal injections induced pressure-independent degeneration of retinal ganglion cells. This indicates the need for indirect stimulation of HSP70 in order to activate their neuroprotective properties. To date, there are insufficient data on the circulation of HSP70 in the body of a person with glaucoma. These data indicate the prospects for further study of the role of HSP70 in glaucoma degeneration and elucidation of the ways of their mediated induction. Keywords: heat shock protein, HSP70, glaucoma, ganglion cells, retina, neuroprotection.

Induction of heat shock proteins 27 and 72 in retinal ganglion cells after acute pressure-induced ischaemia

2009 ◽  
Vol 37 (3) ◽  
pp. 299-307 ◽  
Author(s):  
Bettina K Windisch ◽  
Terry L LeVatte ◽  
Michele L Archibald ◽  
Balwantray C Chauhan
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Shock Proteins

scholarly journals Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michal Geva ◽  
Noga Gershoni-Emek ◽  
Luana Naia ◽  
Philip Ly ◽  
Sandra Mota ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Retinal Degeneration ◽  
Retinal Ganglion Cells ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Neuroprotective Effect ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Sigma 1 Receptor ◽  
Sigma 1

AbstractOptic neuropathies such as glaucoma are characterized by retinal ganglion cell (RGC) degeneration and death. The sigma-1 receptor (S1R) is an attractive target for treating optic neuropathies as it is highly expressed in RGCs, and its absence causes retinal degeneration. Activation of the S1R exerts neuroprotective effects in models of retinal degeneration. Pridopidine is a highly selective and potent S1R agonist in clinical development. We show that pridopidine exerts neuroprotection of retinal ganglion cells in two different rat models of glaucoma. Pridopidine strongly binds melanin, which is highly expressed in the retina. This feature of pridopidine has implications to its ocular distribution, bioavailability, and effective dose. Mitochondria dysfunction is a key contributor to retinal ganglion cell degeneration. Pridopidine rescues mitochondrial function via activation of the S1R, providing support for the potential mechanism driving its neuroprotective effect in retinal ganglion cells.

Inherited glaucoma in DBA/2J mice: Pertinent disease features for studying the neurodegeneration

2005 ◽  
Vol 22 (5) ◽  
pp. 637-648 ◽  
Author(s):  
RICHARD T. LIBBY ◽  
MICHAEL G. ANDERSON ◽  
IOK-HOU PANG ◽  
ZACHARY H. ROBINSON ◽  
OLGA V. SAVINOVA ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ganglion Cells ◽  
The Elderly ◽  
Nerve Degeneration ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Future Studies ◽  
Age Related ◽  
Iop Elevation ◽  
Mechanistic Basis

The glaucomas are neurodegenerative diseases involving death of retinal ganglion cells and optic nerve head excavation. A major risk factor for this neurodegeneration is a harmfully elevated intraocular pressure (IOP). Human glaucomas are typically complex, progressive diseases that are prevalent in the elderly. Family history and genetic factors are clearly important in human glaucoma. Mouse studies have proven helpful for investigating the genetic and mechanistic basis of complex diseases. We previously reported inherited, age-related progressive glaucoma in DBA/2J mice. Here, we report our updated findings from studying the disease in a large number of DBA/2J mice. The period when mice have elevated IOP extends from 6 months to 16 months, with 8–9 months representing an important transition to high IOP for many mice. Optic nerve degeneration follows IOP elevation, with the majority of optic nerves being severely damaged by 12 months of age. This information should help with the design of experiments, and we present the data in a manner that will be useful for future studies of retinal ganglion cell degeneration and optic neuropathy.

Co-expression of heat shock transcription factors 1 and 2 in rat retinal ganglion cells

2006 ◽  
Vol 405 (3) ◽  
pp. 191-195 ◽  
Author(s):  
Jacky M.K. Kwong ◽  
Maziar Lalezary ◽  
Jessica K. Nguyen ◽  
Christine Yang ◽  
Anuj Khattar ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Heat Shock ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Heat Shock Transcription Factors

scholarly journals PTEN Expression Regulates Gap Junction Connectivity in the Retina

2021 ◽  
Vol 15 ◽  
Author(s):  
Ashley M. Chen ◽  
Shaghauyegh S. Azar ◽  
Alexander Harris ◽  
Nicholas C. Brecha ◽  
Luis Pérez de Sevilla Müller
Keyword(s):  
Gap Junction ◽  
Retinal Ganglion Cells ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Dendritic Structure ◽  
Amacrine Cells ◽  
Mouse Retina ◽  
Retinal Ganglion ◽  
Cell Coupling ◽  
Cell Degeneration

Manipulation of the phosphatase and tensin homolog (PTEN) pathway has been suggested as a therapeutic approach to treat or prevent vision loss due to retinal disease. In this study, we investigated the effects of deleting one copy of Pten in a well-characterized class of retinal ganglion cells called α-ganglion cells in the mouse retina. In Pten+/– retinas, α-ganglion cells did not exhibit major changes in their dendritic structure, although most cells developed a few, unusual loop-forming dendrites. By contrast, α-ganglion cells exhibited a significant decrease in heterologous and homologous gap junction mediated cell coupling with other retinal ganglion and amacrine cells. Additionally, the majority of OFF α-ganglion cells (12/18 cells) formed novel coupling to displaced amacrine cells. The number of connexin36 puncta, the predominant connexin that mediates gap junction communication at electrical synapses, was decreased by at least 50% on OFF α-ganglion cells. Reduced and incorrect gap junction connectivity of α-ganglion cells will affect their functional properties and alter visual image processing in the retina. The anomalous connectivity of retinal ganglion cells would potentially limit future therapeutic approaches involving manipulation of the Pten pathway for treating ganglion cell degeneration in diseases like glaucoma, traumatic brain injury, Parkinson’s, and Alzheimer’s diseases.

scholarly journals Induction of Heat Shock Protein-72 by Magnetic Nanofluid Hyperthermia in Cultured Retinal Ganglion Cells for Neuroprotective Treatment in Glaucoma

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jin Wook Jeoung ◽  
Minhong Jeun ◽  
Joo Hyun Park ◽  
Yu Jeong Kim ◽  
Seongtae Bae ◽  
...  
Keyword(s):  
Heat Shock ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Magnetic Hyperthermia ◽  
Immunofluorescent Staining ◽  
Target Tissue ◽  
Retinal Ganglion ◽  
Magnetic Nanofluid ◽  
Neuroprotective Treatment ◽  
Magnetic Nanofluid Hyperthermia

Background. Magnetic hyperthermia using superparamagnetic nanoparticle (SPNP) agents is considered a promising biotechnological approach to induce heat shock proteins (HSPs) in a target tissue because it can generate accurately controllable localized heating.Objectives. The main objective of this study is to demonstrate induction of HSPs in cultured retinal ganglion cells (RGCs) by using engineered Mn0.5Zn0.5Fe2O4SPNP agents coated with polyethylene glycol (PEG) 500.Methods. The Mn0.5Zn0.5Fe2O4nanoparticles were synthesized using a high temperature thermal decomposition method. The AC heating characteristics of PEG 500-coated Mn0.5Zn0.5Fe2O4nanoparticles were investigated using an AC solenoid coil-capacitor system.Results. PEG 500-coated SPNPs efficiently penetrated into the cytoplasm of RGCs without causing obvious cytological changes and showed stable and well-saturated self-heating temperature rise characteristics. Immunofluorescent staining images showed that AC magnetic hyperthermia successfully induced HSP72 in RGCs incubated with Mn0.5Zn0.5Fe2O4nanoparticles. In Western blot analysis, a significant increase in immunoreactivity was observed for RGCs incubated with SPNPs in a fixed AC magnetic field (fappl=140 kHz andHappl=140 Oe).Conclusion. Our results demonstrate that the induction of HSP72 with a magnetic nanofluid hyperthermia could potentially be used as a neuroprotective treatment modality by way of enhancing a natural cytoprotective response.

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