Selective inner retinal dysfunction in growth hormone transgenic mice

Abstract

ObjectiveThe discovery of locally produced growth hormone (GH) and its receptor in the retina of rodents raises the possibility that GH might modulate retinal function. To test this hypothesis, we determined the retinal electroretinogram (ERG) of bovine GH (bGH) transgenic mice. DesignERGs were recorded from 11 wild type (WT) and 9 bGH mice, at 2months of age in response to a series of light flashes at increasing intensity. Three ERG components were assessed for their amplitude and timing: a-wave, b-wave and oscillatory potentials (OPs). OPs were isolated with a 75–300Hz digital filter. Retina layer sizes, nuclei number and vascularization were assessed by respectively staining cross sections with DAPI and Bandeiraea simplicifolia. ResultsOPs were selectively affected in the bGH mouse compared to WT. When OP amplitude values were normalized to the a-wave amplitude (to account for inter-animal variability in WT and bGH groups), OP2, OP3, and OP4 showed amplitude reductions (of 65%, 72%, and 68%, respectively) in the bGH mouse compared to the WT. This was accompanied by a prolongation of the implicit time for the peak of OP3 (28.1 vs 31.1ms, WT vs bGH) and OP4 (37.8 vs 41.6ms), while the implicit time of a- and b-waves were unaffected. Fast Fourier transform analysis revealed that the OPs' dominant frequency was significantly reduced (P<0.05) in the bGH mice (100Hz) compared to WT (108Hz). There was no significant change in retinal histology except for a significant increase in the axial length of the eye in bGH mice. ConclusionsMice expressing bGH display a selective inner retinal defect as demonstrated using ERG recordings. The specific OP defect observed in these mice is similar to the ERG results obtained in patients with diabetic retinopathy and in related animal models.