Abstract
Purpose: :
STAT1 is a member of Signal Transducers and Activators of Transcription multifamily and is originally identified as a major mediator for interferon gamma signaling. In our previous studies we found that STAT1 protein is profoundly expressed in the inner and outer plexform layers of mouse retina, which suggested STAT1 is associated with neuron synaptic transmission. This function of STAT1 has not been reported before. In this study, we have used electroretinogram (ERG) and histological methods to reveal the role of STAT1 in retina.
Methods: :
The eyes of STAT1 deficient mice at different ages were examined and compared with eyes of age-matched C57Bl/6j wild type controls (Jackson Laboratory). Animal protocols were in accordance with ARVO guidelines. The ERG recordings were used an established method (Vistamehr, 2004) with modification. Briefly, after dark adaptation, the contact electrodes were applied to the corneas of anesthetized mice. ERGs were evoked by 100ms white flashes generated by light-emitting diode (LED) arrays built into a pair of miniature Ganzfield stimulators for both eyes (EPIC-3000, LKC Technologies Inc., Gaithersburg, MD). The amplitudes ERG components a-wave, b-wave and oscillatory potentials were measured. A student t-test analysis was used to examine the amplitudes difference among these strains. STAT1 deficient mice at different ages and age-matched C57Bl/6j wild type were euthenized. For electron microscopic study, fresh isolated eyecups were fixed following standard protocol. The tissues were chopped into 1mm3 cubes, went through dehydrate and were embedded in Epon. Images were taken by transmission electron microscope (Tecnai 12 Biotwin, Philips).
Results: :
Compared with their age-matched C57Bl/6j controls, a significant reduction of oscillatory potential (p<0.001) is observed in the eyes from STAT1 deficient mice (n=12) compared with wild type controls (n=25) while a-wave and b-wave are under normal ranges at age of 5 months. A significant reduction of oscillatory potential (p<0.05) can be found in STAT1 deficient eyes (n=14) compared with control eyes (n=18) as early as age PN20. The oscillatory potential, which reflects interactions among bipolar, amacrine, and ganglion cells, is a functional measurement of inner plexform and retina layers. Under electron microscope, a morphologic change in retinal inner plaxform layer of STAT1 deficient retina was found, but without obvious light microscopic alteration.
Conclusions: :
These results provided strong evidences, which support a novel role of STAT1 in retina neuron functions. The mechanisms of STAT1 on retina neurons remain to be determined.
Keywords: electroretinography: non-clinical • transgenics/knock-outs