scholarly journals Cytoprotective Effect of Astaxanthin in a Model of Normal Intraocular Pressure Glaucoma

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Kasumi Kikuchi ◽  
Zhenyu Dong ◽  
Yasuhiro Shinmei ◽  
Miyuki Murata ◽  
Atsuhiro Kanda ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Ganglion Cells ◽  
Normal Tension Glaucoma ◽  
Nerve Degeneration ◽  
Retinal Ganglion ◽  
Cytoprotective Effect ◽  
Littermate Control ◽  
Stress Effects ◽  
Antioxidative Stress ◽  
Hematoxylin And Eosin

Glaucoma is characterized by axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies. Lowering intraocular pressure is currently the only way to treat glaucoma, but it is often insufficient to inhibit the progression of the disease. Glaucoma is a multifactorial disease, and the involvement of oxidative stress has recently received much attention. In the present study, we investigated the cytoprotective effect of astaxanthin (AST) on RGC degeneration using a normal-tension glaucoma (NTG) mouse model, which lacks the glutamate/aspartate transporter (Glast) and demonstrates spontaneous RGC and optic nerve degeneration without elevated intraocular pressure. Three-week-old Glast± mice were given intraperitoneal injections of AST at 10, 30, or 60 mg/kg/day or vehicle alone, and littermate control mice were given vehicle alone for 14 days, respectively. Five weeks after birth, the number of RGCs was counted in paraffin sections of retinal tissues stained with hematoxylin and eosin. We also used a retrograde labeling technique to quantify the number of RGCs. Additionally, the phosphorylated (p) IκB/total IκB ratio and the 4-hydroxynonenal (HNE) were measured in retinal tissues. The number of RGCs in Glast± mice was significantly decreased compared with that in control mice. RGC loss was suppressed by the administration of AST at 60 mg/kg/day, compared with vehicle alone. Following AST administration, the concentration of 4-HNE in the retina was also suppressed, but the pIκB/IκB ratio did not change. Our study revealed that the antioxidative stress effects of AST inhibit RGC degeneration in the retina and may be useful in the treatment of NTG.

scholarly journals Oral pyruvate prevents glaucomatous neurodegeneration

2020 ◽  
Author(s):  
Pete A Williams ◽  
Jeffrey M Harder ◽  
Chelsea Guymer ◽  
John P M Wood ◽  
Evangelia Daskalaki ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Ganglion Cells ◽  
Nerve Degeneration ◽  
Columbia University ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Oral Supplementation ◽  
Pressure Sensitive ◽  
Age Related ◽  
Clinical Models

AbstractIntraocular pressure-sensitive retinal ganglion cell degeneration is a hallmark of glaucoma, the leading cause of irreversible blindness. Converging evidence indicates that age-related bioenergetic insufficiency increases the vulnerability of retinal ganglion cells to intraocular pressure. To investigate further, we used metabolomics and RNA-sequencing to examine early glaucoma in DBA/2J mice. We demonstrate an intraocular pressure-dependent decline in retinal pyruvate levels coupled to dysregulated glucose metabolism prior to detectable optic nerve degeneration. Oral supplementation of pyruvate strongly protected from neurodegeneration in pre-clinical models of glaucoma. We detected mTOR activation at the mechanistic nexus of neurodegeneration and metabolism. Rapamycin-induced inhibition of mTOR robustly prevented glaucomatous neurodegeneration. Bioenergetic enhancement, in combination with intraocular pressure reduction, therefore provides a readily translatable strategy that warrants investigation in clinical trials.FundingVetenskapsrådet 2018-02124 and StratNeuro StartUp grant (PAW). Pete Williams is supported by the Karolinska Institutet in the form of a Board of Research Faculty Funded Career Position and by St. Erik Eye Hospital philanthropic donations. EY011721 and the Barbra and Joseph Cohen Foundation and startup funds from Columbia University (SWMJ). Simon John is an Investigator of HHMI.

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.

scholarly journals Effect of Acupuncture on Intraocular Pressure in Glaucoma Patients: A Single-Blinded, Randomized, Controlled Trial

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Shu-Yuan Chen ◽  
Feng-Shuen Yieh ◽  
Wen-Ling Liao ◽  
Tsai-Chung Li ◽  
Ching-Liang Hsieh
Keyword(s):  
Randomized Controlled Trial ◽  
Intraocular Pressure ◽  
Sham Group ◽  
Ganglion Cells ◽  
Controlled Trial ◽  
Ocular Blood Flow ◽  
Retinal Ganglion ◽  
Randomized Controlled ◽  
Ocular Perfusion ◽  
The Difference

Glaucoma is characterized by the degeneration of retinal ganglion cells that cause progressive optic neuropathy, finally resulting in changes to the optic nerve head. Lowering intraocular pressure (IOP) is the only method proven for treating glaucoma. Several studies have discovered that acupuncture can reduce IOP and also increase ocular perfusion and ocular blood flow. Therefore, the present study investigated the effect of acupuncture on IOP in glaucoma patients. We conducted a single-blinded, randomized, controlled trial involving 45 glaucoma patients. The results indicated that the difference between the IOP 60 min after the intervention and IOP immediately before the intervention was greater in the acupuncture group (AG) and electroacupuncture group (EG) than in the sham group (SG) for all four of the interventions performed and in both eyes (all p<0.05). The IOP difference between immediately before the first intervention and after finishing the final intervention was also greater in the AG and EG than in the SG in both eyes (all p<0.05). In conclusion, IOP was reduced at 60 min after acupuncture or electroacupuncture was performed at BL1 and EX-HN7. Additionally, IOP was reduced after finishing four acupuncture or electroacupuncture sessions. Therefore, our results suggest that acupuncture and electroacupuncture are beneficial for lowering IOP in glaucoma patients. This trial is registered with NCT04157530.

scholarly journals Disturbed glucose and pyruvate metabolism in glaucoma with neuroprotection by pyruvate or rapamycin

2020 ◽  
Vol 117 (52) ◽  
pp. 33619-33627
Author(s):  
Jeffrey M. Harder ◽  
Chelsea Guymer ◽  
John P. M. Wood ◽  
Evangelia Daskalaki ◽  
Glyn Chidlow ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Nerve Degeneration ◽  
Retinal Ganglion ◽  
Metabolic Disturbances ◽  
Pyruvate Metabolism ◽  
Cell Degeneration ◽  
Oral Supplementation ◽  
Impact Pathways ◽  
Glucose Levels ◽  
Pressure Sensitive

Intraocular pressure-sensitive retinal ganglion cell degeneration is a hallmark of glaucoma, the leading cause of irreversible blindness. Here, we used RNA-sequencing and metabolomics to examine early glaucoma in DBA/2J mice. We demonstrate gene expression changes that significantly impact pathways mediating the metabolism and transport of glucose and pyruvate. Subsequent metabolic studies characterized an intraocular pressure (IOP)-dependent decline in retinal pyruvate levels coupled to dysregulated glucose metabolism prior to detectable optic nerve degeneration. Remarkably, retinal glucose levels were elevated 50-fold, consistent with decreased glycolysis but possibly including glycogen mobilization and other metabolic changes. Oral supplementation of the glycolytic product pyruvate strongly protected from neurodegeneration in both rat and mouse models of glaucoma. Investigating further, we detected mTOR activation at the mechanistic nexus of neurodegeneration and metabolism. Rapamycin-induced inhibition of mTOR robustly prevented glaucomatous neurodegeneration, supporting a damaging role for IOP-induced mTOR activation in perturbing metabolism and promoting glaucoma. Together, these findings support the use of treatments that limit metabolic disturbances and provide bioenergetic support. Such treatments provide a readily translatable strategy that warrants investigation in clinical trials.

scholarly journals Neuroprotective and Anti-Inflammatory Effects of a Hydrophilic Saffron Extract in a Model of Glaucoma

2019 ◽  
Vol 20 (17) ◽  
pp. 4110 ◽  
Author(s):  
Jose A. Fernández-Albarral ◽  
Ana I. Ramírez ◽  
Rosa de Hoz ◽  
Nerea López-Villarín ◽  
Elena Salobrar-García ◽  
...  
Keyword(s):  
Cell Death ◽  
Intraocular Pressure ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Retinal Ganglion Cell Death ◽  
Saffron Extract ◽  
Anti Inflammatory ◽  
Ganglion Cell Death

Glaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells (RGCs). An increase in the intraocular pressure is the principal risk factor for such loss, but controlling this pressure does not always prevent glaucomatous damage. Activation of immune cells resident in the retina (microglia) may contribute to RGC death. Thus, a substance with anti-inflammatory activity may protect against RGC degeneration. This study investigated the neuroprotective and anti-inflammatory effects of a hydrophilic saffron extract standardized to 3% crocin content in a mouse model of unilateral, laser-induced ocular hypertension (OHT). Treatment with saffron extract decreased microglion numbers and morphological signs of their activation, including soma size and process retraction, both in OHT and in contralateral eyes. Saffron extract treatment also partially reversed OHT-induced down-regulation of P2RY12. In addition, the extract prevented retinal ganglion cell death in OHT eyes. Oral administration of saffron extract was able to decrease the neuroinflammation associated with increased intraocular pressure, preventing retinal ganglion cell death. Our findings indicate that saffron extract may exert a protective effect in glaucomatous pathology.

Next-Generation Techniques for Analysis of Lamina Cribrosa Microstructure

2012 ◽  
Author(s):  
C. Ross Ethier ◽  
Richie Abel ◽  
E. A. Sander ◽  
John G. Flanagan ◽  
Michael Girard
Keyword(s):  
Risk Factor ◽  
Intraocular Pressure ◽  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Ganglion Cells ◽  
Lamina Cribrosa ◽  
Retinal Ganglion ◽  
Irreversible Damage ◽  
Ocular Disorders ◽  
The Brain

Glaucoma describes a group of potentially blinding ocular disorders, afflicting c. 60 million people worldwide. Of these, c. 8 million are bilaterally blind, estimated to increase to 11 million by 2020. The central event in glaucoma is slow and irreversible damage of retinal ganglion cells, responsible for carrying visual information from the retina to the brain (Figure 1). Intraocular pressure (IOP) is a risk factor for glaucoma1–4, and significant, sustained IOP reduction is unequivocally beneficial in the clinical management of glaucoma patients2, 3, 5. Unfortunately, we do not understand how elevated IOP leads to the loss of retinal ganglion cells.

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