Purchase this article with an account.
Y. Ha, A. Saul, E. Zorrilla, V. Ganapathy, S. B. Smith; Functional and Morphological Analysis of Retinas of Sigma Receptor 1 (R1) Null Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3711.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
σR1 is thought to act as a molecular chaperone at the ER membrane. Recently, we reported robust protection against retinal ganglion cell (RGC) death when a σR1-specific ligand was administered to diabetic mice (Smith et al, 2008). To understand how σR1 mediates retinal neuroprotection, we established a colony of σR1 null (-/-) mice to examine the retinal phenotype functionally and histologically as there have been no reports of the consequence to retina when σR1 is not present.
A colony of σR1 wildtype (+/+), heterozygous (+/-) and homozygous (-/-) mice were established. Neural retina and brain were subjected to RT-PCR, western blotting (WB) and immunohistochemistry (IHC) to analyze expression of σR1. Mice (age: 5-6 wks) were tested in scotopic/photopic conditions at a range of flash intensities after 12 h dark adaptation. Eyes were processed for light microscopy to assess retinal morphology.
RT-PCR and WB confirmed abundant σR1 gene/protein expression in retina, brain and other tissues of σR1 +/+ mice, but not σR1 -/- mice. IHC detected σR1 in several retinal layers in +/+ mice, but not in σR1 -/- mice. Scotopic ERGs revealed implicit times ranging from ~40-15 ms for a-waves, ~100-60 ms for b-waves. Responses for +/+, +/- and -/- mice were within normal ranges (strong b-waves and OPs, strong a-waves at high intensities), however the amplitudes in σR1 -/- mice were weaker than +/+ or +/- mice. Morphologically, retinas of σR1 -/- mice were comparable to σR1 +/+ and +/- mice (total retinal thickness = ~ 250 µm, INL = ~35-40 µm, ~12-14 rows of PRC nuclei, ~15 RGCs/100 µm retinal length).
This is the first analysis of retinas of mice lacking σR1. The data suggest that, at least at early ages, σR1 -/- mice have retinal morphology and function similar to wildtype. Studies are underway to assess the long-term effects of the lack of σR1 gene on retinal morphology, function and expression of ER stress genes and will set the stage for mechanistic studies to determine how σR1 mediates neuroprotection in diabetes.
This PDF is available to Subscribers Only