June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Altered Glutamate Cysteine Ligase Expression In The Retina Of Two Retinitis Pigmentosa Animal Models
Author Affiliations & Notes
  • Maria Miranda
    Physiology, Univ CEU-Cardenal Herrera, Moncada, Valencia, Spain
  • Soledad Benlloch-Navarro
    Physiology, Univ CEU-Cardenal Herrera, Moncada, Valencia, Spain
  • Laura Traschel-Moncho
    Physiology, Univ CEU-Cardenal Herrera, Moncada, Valencia, Spain
  • Francisco J Romero
    Facultad de Medicina, Universidad Católica de Valencia ‘San Vicente Mártir’, Valencia, Spain
  • Javier J Araiz
    Ophthalmology Dept, School of Medicine and Dentistry, University of the Basque Country, Leioa, Spain
    R & D Dept, Instituto Clínico-Quirúrgico de Oftalmologia, Bilbao, Spain
  • Footnotes
    Commercial Relationships Maria Miranda, None; Soledad Benlloch-Navarro, None; Laura Traschel-Moncho, None; Francisco Romero, None; Javier Araiz, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4663. doi:
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      Maria Miranda, Soledad Benlloch-Navarro, Laura Traschel-Moncho, Francisco J Romero, Javier J Araiz; Altered Glutamate Cysteine Ligase Expression In The Retina Of Two Retinitis Pigmentosa Animal Models. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4663.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Retinitis Pigmentosa (RP) includes a group of inherited retinal diseases in which one of several different mutations results in death of photoreceptors. Our group and others have demonstrated that oxidative stress, and particularly alterations in glutathione (GSH), may be important in the pathogenesis of RP as photoreceptor death can be exacerbated by oxidative stress.<br /> Herein, we tested whether the expression of glutamate cysteine ligase (GCL), the rate limiting enzyme in GSH synthesis, is altered in the retina of different RP animal models. GCL is composed of two subunits. One subunit (GCLC) is the relatively heavy (73 kDa) subunit, which has catalytic activity and can be inhibited by GSH. The lower molecular weight (28 kDa) subunit (GCLM) is enzymatically inactive but regulates the activity of the enzyme by reducing the inhibition by GSH.

Methods: Animals were treated in accordance to the ARVO statement for the use of animals in ophthalmic and vision research. We obtained retinas from C3H and rd1 mice at different postnatal days (PN7, 11, 15, 17, 19, 21 and 28), and from C57BL and rd10 mice at PN21. Western blot analysis and inmunohistochemistry was performed to assess expression of GCLC and GCLM, antibodies for these two enzymes were purchased from Abcam (Cambridge, MA).

Results: The expression of GCLC decreased with age in both C3H and rd1 mice, however, after the peak of photoreceptor death (PN 19, 21 and 28) there was an increase in the expression of GCLC in rd1 mice when compared to control ones. There was no change in GCLM with age, and no difference was observed between strains, but the ratio GCLM/GCLC was decreased in rd1 mice at PN21 and 28. GCLC was also increased in the retina of rd10 mice at PN21 (p<0,05). GCLC expression was observed mainly in Müller cells, and occasionally in some horizontal and ganglion cells in control mice. In the retina of rd1 and specially in rd10 mice GCLC was widely expressed in Müller cells, but also in the plexiform layers and in ganglion cells.

Conclusions: Our results confirm our previous findings that confirmed an increase of GSH after the peak of cell death in these two models of RP. It has been suggested that oxidative stress can induce GCL. In this case, the oxidant situation that is present in these retinas may be the responsible for the increase in GCL, though further studies are needed to confirm this hypothesis.


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