Interleukin-1 attenuates normal tension glaucoma-like retinal degeneration in EAAC1-deficient mice.

Abstract

Glaucoma, one of the leading causes of irreversible blindness, is characterized by progressive degeneration of retinal ganglion cells (RGCs) and optic nerves. Although glaucoma is often associated with elevated intraocular pressure, recent studies have shown a relatively high prevalence of normal tension glaucoma (NTG) in glaucoma patient populations. In the mammalian retina, glutamate/aspartate transporter (GLAST) is localized to Müller glial cells, whereas excitatory amino acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs. Since the loss of GLAST or EAAC1 leads to retinal degeneration similar to that seen in NTG, we examined the effects of interleukin-1 (IL-1) on RGC death in GLAST- and EAAC1-deficient mice. IL-1 promoted increased glutamate uptake in Müller cells by suppressing intracellular Na(+) accumulation, which is necessary to counteract Na(+)-glutamate cotransport. The observed trends for the glutamate uptake increase in the wild-type (WT), GLAST- and EAAC1-deficient mice were similar; however, the baseline glutamate uptake and intracellular Na(+) concentration in the GLAST-deficient mice were significantly lower than those in the wild-type mice. Consistently, pretreatment with IL-1 exhibited no beneficial effects on glutamate-induced RGC degeneration in the GLAST-deficient mice. In contrast, IL-1 significantly increased glutamate uptake by Müller cells and the number of surviving RGCs in the wild-type and EAAC1-deficient mice. Our findings suggest that the use of IL-1 for enhancing the function of glutamate transporters may be useful for neuroprotection in retinal degenerative disorders including NTG.

• Authors: Kazuhiko Namekata, Chikako Harada, Xiaoli Guo, Kenji Kikushima, Atsuko Kimura, Nobuo Fuse, Yoshinori Mitamura, Kuniko Kohyama, Yoh Matsumoto, Kohichi Tanaka, Takayuki Harada
• Journal: Neuroscience letters (Neurosci Lett) Vol. 465 Issue 2 Pg. 160-4 (Nov 13 2009) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 19766171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Excitatory Amino Acid Transporter 1
• Excitatory Amino Acid Transporter 3
• Interleukin-1
• Slc1a1 protein, mouse
• Slc1a3 protein, mouse
• Glutamic Acid
• Sodium

Topics

• Animals
• Cell Death (physiology)
• Cell Survival (physiology)
• Excitatory Amino Acid Transporter 1 (deficiency, genetics, metabolism)
• Excitatory Amino Acid Transporter 3 (deficiency, genetics, metabolism)
• Glaucoma (physiopathology)
• Glutamic Acid (metabolism)
• Interleukin-1 (metabolism)
• Intracellular Space (metabolism)
• Intraocular Pressure
• Mice
• Mice, Knockout
• Neuroglia (physiology)
• Retina (physiopathology)
• Retinal Degeneration (physiopathology)
• Retinal Ganglion Cells (physiology)
• Sodium (metabolism)