Light-Evoked Responses of the Mouse Retinal Pigment Epithelium

Abstract

In response to light, the retinal pigment epithelium (RPE) generates a series of slow potentials that can be recorded as the c-wave, fast oscillation (FO), and light peak (LP) of the electroretinogram (ERG). As these potentials can be related to specific cellular events, they provide information about RPE function and how that may be altered by disease or experimental manipulation. In the present study we describe a noninvasive means for recording the light-evoked responses of the mouse RPE and use this to define the stimulus-response properties of the major components in three inbred strains of mice (BALBc/ByJ, C57BL/6J, and 129/SvJ) and two mouse mutants that reduce activity in the rod pathway. All of the major ERG components generated by the RPE are readily measured in the mouse. In albino strains (BALBc/ByJ and 129/SvJ) the intensity-response functions for the c-wave, FO, and LP are shifted toward lower intensities in comparison to those for C57BL/6J mice. Each of these components was markedly reduced in mice lacking transducin in which rod phototransduction is interrupted, indicating that they reflect primarily rod photoreceptor activity. All components were observed in no b-wave ( nob) mutant mice, indicating that inner retinal activity does not make a major contribution to these potentials. Further studies of mutant mice will allow us to define the functional consequences of gene manipulation on RPE function and to evaluate specific hypotheses regarding the generation of ERG components.

A potential mouse model for the erosive vitreoretinopathy of Wagner disease      

“…After the last time point, 12 animals (6 wild type and 6 hdf +/-mice) were sacrificed and eyes were removed for morphological analysis at the Institute of Medical and Molecular Genetics, University of Zurich. Histology Eyes were fixed and embedded in paraffin, and 2-3 µm sections were cut and were stained with haematoxylin-eosin as described [18]. Analysis was performed using Zeiss Axioplan2 imaging light microscopy.…”

“…Furthermore, ophthalmoscopic analysis of wild type and mutant mice at 5.5 months did not reveal a difference (data not shown). At age 17 months, in the mutant animal eyes, the b-wave amplitude of the scotopic ERG was significantly reduced by 22% on average ( in addition to photoreceptors and inner layer of retina, the retinal pigment epithelium (RPE) is also involved [18].…”

Light-Evoked Responses of the Retinal Pigment Epithelium: Changes Accompanying Photoreceptor Loss in the Mouse

“…To measure ERG components generated by the RPE, we used a previously established protocol adapted for mouse recording (Wu et al 2004b). Briefly, responses were obtained from the corneal surface of the left eye using an unpulled 1-mm-diameter borosilicate capillary tube with filament (BF100-50-10; Sutter Instrument, Novato, CA).…”

“…Despite being evoked by light stimuli, none of the dc-ERG components reflects a direct response of the RPE to light. Instead, each is generated secondary to rod photoreceptor activity (Steinberg 1985;Wu et al 2004b). The initial c-wave reflects the interaction of two signals.…”

“…Because each dc-ERG component is generated secondarily to rod photoreceptor activation (Wu et al 2004b), interpretation of dc-ERG components is most straightforward when the activity of rod photoreceptors (reflected in the ERG a-wave) is maintained at a normal level Wu et al , 2007. As noted earlier, however, many mouse models of RPE gene defects are associated with rod photoreceptor degeneration, which will alter the rod photoreceptorderived signal delivered to the RPE and thus the generation of each dc-ERG component.…”