Localization and regulation of glucagon receptors in the chick eye and preproglucagon and glucagon receptor expression in the mouse eye

Feldkaemper, Marita; Burkhardt, Eva; Schaeffel, Frank

doi:10.1016/j.exer.2004.04.009

Cited by 20 publications

(12 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among its actions, the glucagon receptor under control of glucagon regulates gluconeogenesis to increase BG levels. Liver and kidney abundantly express Gcgr, and PCR analysis reveals trace levels of receptor mRNA in the retina of wild-type (WT) mice (14), a result we confirm (data not shown). Adult Gcgr Ϫ/Ϫ mice exhibited a BG range of 50-115 mg/dl (see Methods) with a mean Ϯ SD of 78.4 Ϯ 16.9 mg/dl (11-13 months of age, n ϭ 14).…”

Section: Glucagon Receptor and Changes In Bgsupporting

confidence: 71%

Hypoglycemia leads to age-related loss of vision

Umino

Everhart

Solessio

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The retina is among the most metabolically active tissues in the body, requiring a constant supply of blood glucose to sustain function. We assessed the impact of low blood glucose on the vision of C57BL/6J mice rendered hypoglycemic by a null mutation of the glucagon receptor gene, Gcgr. Metabolic stress from moderate hypoglycemia led to late-onset loss of retinal function in Gcgr ؊/؊ mice, loss of visual acuity, and eventual death of retinal cells. Retinal function measured by the electroretinogram b-wave threshold declined >100-fold from age 9 to 13 months, whereas decreases in photoreceptor function measured by the ERG a-wave were delayed by 3 months. At 10 months of age Gcgr ؊/؊ mice began to lose visual acuity and exhibit changes in retinal anatomy, including an increase in cell death that was initially more pronounced in the inner retina. Decreases in retinal function and visual acuity correlated directly with the degree of hypoglycemia. This work demonstrates a metabolic-stress-induced loss of vision in mammals, which has not been described previously. Linkage between low blood glucose and loss of vision in mice may highlight the importance for glycemic control in diabetics and retinal diseases related to metabolic stress as macular degeneration.C57BL/6J mice ͉ cell death ͉ glucagon receptor gene ͉ retinal function ͉ visual acuity C hanges in metabolism can affect vision. Lowering blood glucose (BG) can decrease human visual sensitivity (1-3) as does reducing the partial pressure of inhaled oxygen (4). Natural nighttime decreases in glucose availability (5, 6) parallel a decline in visual sensitivity that can be restored by glucose ingestion (7). In the cat, acute decreases in glucose supply can transiently reduce retinal sensitivity (8) and exacerbate the effects of hypoxia on the retina (9). The effects of metabolite supply on vision are not surprising in view of the high energy consumption by the retina (10, 11). Although the retina's high metabolic activity has been known for Ͼ40 years (12), the consequences of an inadequate supply of metabolites are not completely understood.We report here that a chronic decrease in BG in mice decreases retinal function, leading to a loss of vision and eventual degeneration of the retina. We observed decreases in both electroretinogram (ERG) a-and b-waves, as well as a loss in visual acuity. Retinal cell death, assayed by TUNEL, was increased in Gcgr Ϫ/Ϫ mice, and decreases in cell number were detected. These data indicate that a chronic decrease in BG leads to loss of vision and cell death in mice and highlight the possibility that the human retina may likewise be susceptible to hypoglycemia. ResultsGlucagon Receptor and Changes in BG. Hypoglycemia was induced in C57BL/6J mice by a null mutation of the glucagon receptor gene, Gcgr (13). Among its actions, the glucagon receptor under control of glucagon regulates gluconeogenesis to increase BG levels. Liver and kidney abundantly express Gcgr, and PCR analysis reveals trace levels of receptor mRNA in the retina of wi...

show abstract

Section: Glucagon Receptor and Changes In Bgsupporting

confidence: 71%

Hypoglycemia leads to age-related loss of vision

Umino

Everhart

Solessio

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The CGACs and glucagon peptide in the avian eye have been shown to participate in vision-guided ocular growth, which occurs during postnatal development (Fischer et al, 1999b;Bitzer and Schaeffel, 2002;Feldkaemper and Schaeffel, 2002;Feldkaemper et al, 2004). We have reported previously that the glucagoncontaining amacrine cells in the chicken retina respond to lensimposed hyperopia (which stimulates ocular growth) by decreasing expression levels of the immediate-early gene early growth response gene 1 (Egr1), whereas levels of Egr1 are increased in response to lens-imposed myopia (Fischer et al, 1999b).…”

Section: Discussionmentioning

confidence: 99%

Glucagon-Expressing Neurons within the Retina Regulate the Proliferation of Neural Progenitors in the Circumferential Marginal Zone of the Avian Eye

Fischer

Omar²,

Walton³

et al. 2005

J. Neurosci.

View full text Add to dashboard Cite

Glucagon-expressing retinal amacrine cells have been implicated in regulating postnatal ocular growth. Furthermore, experimentally accelerated rates of ocular growth increase the number of neurons added to the peripheral edge of the retina. Accordingly, we assayed whether glucagon-expressing neurons within the retina regulate the proliferation of progenitors in the circumferential marginal zone (CMZ) of the postnatal chicken eye. We found that glucagon-containing neurites are heavily clustered within the CMZ at the peripheral edge of the retina. Many of these neurites originate from a cell type that is distinct from other types of retinal neurons, which we termed large glucagon-expressing neurons (LGENs). The LGENs are immunoreactive for glucagon and glucagon-like peptide 1 (GLP1), have a unipolar morphology, produce an axon that projects into the CMZ, and are found only in ventral regions of the retina. In dorsal regions of the retina, a smaller version of the LGENs densely ramifies neurites in the CMZ. Intraocular injections of glucagon or GLP1 suppressed the proliferation of progenitors in the CMZ, whereas a glucagon-receptor antagonist promoted proliferation. In addition, we found that glucagon, GLP1, and glucagon antagonist influenced the number of progenitors in the CMZ. We conclude that the LGENs may convey visual information to the CMZ to control the addition of new cells to the edge of the retina. We propose that glucagon/GLP1 released from LGENs acts in opposition to insulin (or insulin-like growth factor) to regulate precisely the proliferation of retinal progenitors in the CMZ.

show abstract

Section: Discussionmentioning

confidence: 98%

“…Feldkaemper et al [10] detected small amounts of mRNA for preproglucagon and of the glucagon receptor in the mouse retina, using the more sensitive polymerase chain reaction. On the other hand, preproglucagon could not be detected in the blood [10]. Therefore, it is possible that glucagon is, in fact, produced in retinal cells, but at very low levels, far below the detection limit of our immunohistochemical procedures.…”

Section: Discussionmentioning

confidence: 98%

“…Here, it is localized to glutamic acid decarboxylase-65 immunoreactive amacrine cells (GAD65) rather than to glucagon [42]. Recently, receptors of GLP-2 were localized by immunohistochemical staining in lens and cornea of the mouse [17], and Feldkaemper et al [10] found the mRNA of both the glucagon receptor and of preproglucagon in retina. Therefore, it is possible that another member of the glucagon super family may have taken over the role of glucagon itself in the mechanisms of visual control of eye growth in mammals.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation