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Caloric restriction promotes cell survival in a mouse model of normal tension glaucoma

View Article: PubMed Central - PubMed

ABSTRACT

Glaucoma is characterized by progressive degeneration of retinal ganglion cells (RGCs) and their axons. We previously reported that loss of glutamate transporters (EAAC1 or GLAST) in mice leads to RGC degeneration that is similar to normal tension glaucoma and these animal models are useful in examining potential therapeutic strategies. Caloric restriction has been reported to increase longevity and has potential benefits in injury and disease. Here we investigated the effects of every-other-day fasting (EODF), a form of caloric restriction, on glaucomatous pathology in EAAC1−/− mice. EODF suppressed RGC death and retinal degeneration without altering intraocular pressure. Moreover, visual impairment was ameliorated with EODF, indicating the functional significance of the neuroprotective effect of EODF. Several mechanisms associated with this neuroprotection were explored. We found that EODF upregulated blood β-hydroxybutyrate levels and increased histone acetylation in the retina. Furthermore, it elevated retinal mRNA expression levels of neurotrophic factors and catalase, whereas it decreased oxidative stress levels in the retina. Our findings suggest that EODF, a safe, non-invasive, and low-cost treatment, may be available for glaucoma therapy.

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Related in: MedlinePlus

In vivo imaging of the retina in the control and EODF EAAC1−/− mice.(A) An image of a scanning circle centering around the optic nerve disk. (B) Longitudinal evaluation of the GCC thickness by a circular scan. (C) OCT cross-sectional images of retinas at 5 W and 12 W in mice treated with or without EODF. GCC, ganglion cell complex. (D) Quantitative analyses of GCC thickness of control and EODF mice. The data are presented as means ± SEM of six samples for each experiment. *P < 0.05.
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f3: In vivo imaging of the retina in the control and EODF EAAC1−/− mice.(A) An image of a scanning circle centering around the optic nerve disk. (B) Longitudinal evaluation of the GCC thickness by a circular scan. (C) OCT cross-sectional images of retinas at 5 W and 12 W in mice treated with or without EODF. GCC, ganglion cell complex. (D) Quantitative analyses of GCC thickness of control and EODF mice. The data are presented as means ± SEM of six samples for each experiment. *P < 0.05.

Mentions: We also visualized retinal layers in vivo using SD-OCT78910202122. The average thickness of the ganglion cell complex (GCC), which includes the nerve fiber layer, GCL and the inner plexiform layer, was measured by scanning the retina in a circle centering around the optic nerve disc (Fig. 3A,B). The average thickness of the GCC in the control EAAC1−/− mice without EODF was significantly decreased compared with that in WT mice at 12 W, but such a reduction was significantly suppressed in EODF-treated EAAC1−/− mice (Fig. 3C,D). These data indicate that EODF between 5 W and 12 W suppresses NTG-like retinal degeneration in EAAC1−/− mice.


Caloric restriction promotes cell survival in a mouse model of normal tension glaucoma
In vivo imaging of the retina in the control and EODF EAAC1−/− mice.(A) An image of a scanning circle centering around the optic nerve disk. (B) Longitudinal evaluation of the GCC thickness by a circular scan. (C) OCT cross-sectional images of retinas at 5 W and 12 W in mice treated with or without EODF. GCC, ganglion cell complex. (D) Quantitative analyses of GCC thickness of control and EODF mice. The data are presented as means ± SEM of six samples for each experiment. *P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037377&req=5

f3: In vivo imaging of the retina in the control and EODF EAAC1−/− mice.(A) An image of a scanning circle centering around the optic nerve disk. (B) Longitudinal evaluation of the GCC thickness by a circular scan. (C) OCT cross-sectional images of retinas at 5 W and 12 W in mice treated with or without EODF. GCC, ganglion cell complex. (D) Quantitative analyses of GCC thickness of control and EODF mice. The data are presented as means ± SEM of six samples for each experiment. *P < 0.05.
Mentions: We also visualized retinal layers in vivo using SD-OCT78910202122. The average thickness of the ganglion cell complex (GCC), which includes the nerve fiber layer, GCL and the inner plexiform layer, was measured by scanning the retina in a circle centering around the optic nerve disc (Fig. 3A,B). The average thickness of the GCC in the control EAAC1−/− mice without EODF was significantly decreased compared with that in WT mice at 12 W, but such a reduction was significantly suppressed in EODF-treated EAAC1−/− mice (Fig. 3C,D). These data indicate that EODF between 5 W and 12 W suppresses NTG-like retinal degeneration in EAAC1−/− mice.

View Article: PubMed Central - PubMed

ABSTRACT

Glaucoma is characterized by progressive degeneration of retinal ganglion cells (RGCs) and their axons. We previously reported that loss of glutamate transporters (EAAC1 or GLAST) in mice leads to RGC degeneration that is similar to normal tension glaucoma and these animal models are useful in examining potential therapeutic strategies. Caloric restriction has been reported to increase longevity and has potential benefits in injury and disease. Here we investigated the effects of every-other-day fasting (EODF), a form of caloric restriction, on glaucomatous pathology in EAAC1&minus;/&minus; mice. EODF suppressed RGC death and retinal degeneration without altering intraocular pressure. Moreover, visual impairment was ameliorated with EODF, indicating the functional significance of the neuroprotective effect of EODF. Several mechanisms associated with this neuroprotection were explored. We found that EODF upregulated blood &beta;-hydroxybutyrate levels and increased histone acetylation in the retina. Furthermore, it elevated retinal mRNA expression levels of neurotrophic factors and catalase, whereas it decreased oxidative stress levels in the retina. Our findings suggest that EODF, a safe, non-invasive, and low-cost treatment, may be available for glaucoma therapy.

No MeSH data available.


Related in: MedlinePlus