Pyroglutamic Acid Promotes Survival of Retinal Ganglion Cells after Optic Nerve Injury

Oono, Shinichirou; Kurimoto, Takuji; Nakazawa, Toru; Miyoshi, Tomomitsu; Okamoto, Norio; Kashimoto, Ryosuke; Tagami, Yuichi; Ito, Yoshimasa; Mimura, Osamu

doi:10.1080/02713680902981292

Cited by 10 publications

(4 citation statements)

References 38 publications

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“…Recently, our group reported that PGA can repair damaged optic nerves. 11) In this study, we investigated the effects of eye drops containing PGA on preventing enhanced IOP in experimentally induced ocular hypertension in rabbits, and found the instillation of eye drops containing PGA reduces the levels of IOP.…”

Section: Discussionmentioning

confidence: 99%

Reduction of Enhanced Rabbit Intraocular Pressure by Instillation of Pyroglutamic Acid Eye Drops

Ito

Nagai

Okamoto

et al. 2013

Biological & Pharmaceutical Bulletin

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l-Pyroglutamic acid (PGA) is an endogenous molecule derived from l-glutamate. We demonstrate the effects of PGA on intraocular pressure (IOP) in experimentally induced ocular hypertension in rabbits. In the in vitro and in vivo transcorneal penetration studies, the PGA solution (PGA in saline) did not penetrate the rabbit cornea. On the other hand, the penetration of PGA was improved by the addition of zinc chloride and 2-hydroxypropyl-β-cyclodextrin (HPCD), and PGA penetration was enhanced with increasing HPCD concentration. Therefore, PGA solutions containing 0.5% zinc chloride and 5% or 10% HPCD (PGA/ HPCD 5% or 10% eye drops) were used to investigate the effects for IOP in this study. An elevation in IOP was induced by the rapid infusion of 5% glucose solution (15 mL/kg of body weight) through the marginal ear vein or maintaining under dark phase for 5 h. In the both models, the induced elevation in IOP was prevented by the instillation of PGA/HPCD eye drops, and the IOP-reducing effect enhanced with increasing HPCD concentration in the drops. Nitric oxide (NO) levels elevated in the aqueous humor following the infusion of 5% glucose solution, and this increase was also suppressed by the instillation of PGA/HPCD eye drops. In conclusion, the present study demonstrates that the instillation of PGA/HPCD eye drops has an IOP-reducing effect in rabbits with experimentally induced ocular hypertension, probably as a result of the suppression of NO production.

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Section: Discussionmentioning

confidence: 99%

Reduction of Enhanced Rabbit Intraocular Pressure by Instillation of Pyroglutamic Acid Eye Drops

Ito

Nagai

Okamoto

et al. 2013

Biological & Pharmaceutical Bulletin

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“…Its neural-specific nature has been used to identify neurons within brain tissues, distinguishing them from glial cells that typically lack Tubb3 expression [140,141]. RGCs exhibit high expression of Tubb3 due to their neuronal origin [142], making it suitable for the identification and quantification of RGCs in different optic nerve injury models [143,144].…”

Section: Molecular Markers For Evaluating Retinal Ganglion Cell Diffe...mentioning

confidence: 99%

Establishing Functional Retina in a Dish: Progress and Promises of Induced Pluripotent Stem Cell-Based Retinal Neuron Differentiation

Wong,

Yip,

Huang

2023

IJMS

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The human eye plays a critical role in vision perception, but various retinal degenerative diseases such as retinitis pigmentosa (RP), glaucoma, and age-related macular degeneration (AMD) can lead to vision loss or blindness. Although progress has been made in understanding retinal development and in clinical research, current treatments remain inadequate for curing or reversing these degenerative conditions. Animal models have limited relevance to humans, and obtaining human eye tissue samples is challenging due to ethical and legal considerations. Consequently, researchers have turned to stem cell-based approaches, specifically induced pluripotent stem cells (iPSCs), to generate distinct retinal cell populations and develop cell replacement therapies. iPSCs offer a novel platform for studying the key stages of human retinogenesis and disease-specific mechanisms. Stem cell technology has facilitated the production of diverse retinal cell types, including retinal ganglion cells (RGCs) and photoreceptors, and the development of retinal organoids has emerged as a valuable in vitro tool for investigating retinal neuron differentiation and modeling retinal diseases. This review focuses on the protocols, culture conditions, and techniques employed in differentiating retinal neurons from iPSCs. Furthermore, it emphasizes the significance of molecular and functional validation of the differentiated cells.

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“…The free form of pyroglutamic acid is present in the brain, eye, and plasma. 8) Although pyroglutamic acid enhances the repair of damaged optic nerves 9) and improves type 2 diabetes, 10) this is the first report which shows that pyroglutamic acid facilitates DNA synthesis in rat primary hepatocytes.…”

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confidence: 99%

Pyroglutamic acid stimulates DNA synthesis in rat primary hepatocytes through the mitogen-activated protein kinase pathway

Inoue

Okita

Toledo

et al. 2015

Bioscience, Biotechnology, and Biochemistry

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We purified pyroglutamic acid from human placental extract and identified it as a potent stimulator of rat primary hepatocyte DNA synthesis. Pyroglutamic acid dose-dependently stimulated DNA synthesis, and this effect was inhibited by PD98059, a dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) inhibitor. Therefore, pyroglutamic acid stimulated DNA synthesis in rat primary hepatocytes via MAPK signaling.

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Pyroglutamic Acid Promotes Survival of Retinal Ganglion Cells after Optic Nerve Injury

Abstract: PGA promotes the survival of axotomized RGCs in adult mammalian retinas possibly mediated by the EAATs.

Cited by 10 publications

References 38 publications

Reduction of Enhanced Rabbit Intraocular Pressure by Instillation of Pyroglutamic Acid Eye Drops

Reduction of Enhanced Rabbit Intraocular Pressure by Instillation of Pyroglutamic Acid Eye Drops

Establishing Functional Retina in a Dish: Progress and Promises of Induced Pluripotent Stem Cell-Based Retinal Neuron Differentiation

Pyroglutamic acid stimulates DNA synthesis in rat primary hepatocytes through the mitogen-activated protein kinase pathway

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