Related Experiment Video
Updated: Jun 3, 2026
Direct-Coupled Electroretinogram (DC-ERG) for Recording the Light-Evoked Electrical Responses of the Mouse Retinal Pigment Epithelium
Published on: July 14, 2020
Effects of subretinal electrical stimulation in mer-KO mice
Julie A Mocko1, Moon Kim, Amanda E Faulkner
1Rehabilitation Research and Development Service, Atlanta Department of Veterans Affairs, Decatur, Georgia 30033, USA.
Purpose:
Subretinal electrical stimulation (SES) from microphotodiode arrays protects photoreceptors in the RCS rat model of retinitis pigmentosa. The authors examined whether mer(kd) mice, which share a Mertk mutation with RCS rats, showed similar neuroprotective effects from SES.
Methods:
Mer(kd) mice were implanted with a microphotodiode array at postnatal day (P) 14. Weekly electroretinograms (ERGs) followed by retinal histology at week 4 were compared with those of age-matched controls. RT-PCR for fibroblast growth factor beta (Fgf2), ciliary nerve trophic factor (Cntf), glial-derived neurotrophic factor (Gdnf), insulin growth factor 1 (Igf1), and glial fibrillary acidic protein (Gfap) was performed on retinas at 1 week after surgery. Rates of degeneration using ERG parameters were compared between mer(kd) mice and RCS rats from P28 to P42.
Results:
SES-treated mer(kd) mice showed no differences in ERG a- and b-wave amplitudes or photoreceptor numbers compared with controls. However, the expression of Fgf2 and Cntf was greater (6.5 ± 1.9- and 2.5 ± 0.5-fold, respectively; P < 0.02) in SES-treated mer(kd) retinas. Rates of degeneration were faster for dark-adapted maximal b-wave, log σ, and oscillatory potentials in mer(kd) mice than in RCS rats.
Conclusions:
Although SES upregulated Fgf2 in mer(kd) retinas, as reported previously for RCS retinas, this was not accompanied by neuroprotection of photoreceptors. Comparisons of ERG responses from mer(kd) mice and RCS rats across different ages showed inner retinal dysfunction in mer(kd) mice but not in RCS rats. This inner retinal dysfunction and the faster rate of degeneration in mer(kd) mice may produce a retinal environment that is not responsive to neuroprotection from SES.
Insights
Subretinal electrical stimulation (SES) did not protect photoreceptors in mer(kd) mice, unlike in RCS rats. Inner retinal dysfunction in mer(kd) mice may prevent SES neuroprotection.
Area of Science:
- Ophthalmology
- Neuroscience
- Genetics
Background:
- Subretinal electrical stimulation (SES) has shown promise in protecting photoreceptors in the Royal College of Surgeons (RCS) rat model of retinitis pigmentosa.
- The Mertk mutation is implicated in both RCS rats and mer(kd) mice, making mer(kd) mice a relevant model to study SES efficacy.
Purpose of the Study:
- To investigate whether SES confers similar neuroprotective effects on photoreceptors in mer(kd) mice as observed in RCS rats.
- To compare the rate of retinal degeneration and electroretinogram (ERG) responses between SES-treated mer(kd) mice and age-matched controls.
Main Methods:
- Mer(kd) mice underwent subretinal microphotodiode array implantation at postnatal day 14.
- Weekly ERGs and terminal retinal histology were performed. RT-PCR analyzed growth factor expression (Fgf2, Cntf, Gdnf, Igf1) and glial fibrillary acidic protein (Gfap).
- Degeneration rates were compared between mer(kd) mice and RCS rats using ERG parameters from P28 to P42.
Main Results:
- SES-treated mer(kd) mice exhibited no significant differences in ERG amplitudes or photoreceptor survival compared to controls.
- Retinal expression of fibroblast growth factor beta (Fgf2) and ciliary nerve trophic factor (Cntf) was upregulated by SES in mer(kd) mice.
- Mer(kd) mice showed faster degeneration rates for specific ERG parameters compared to RCS rats.
Conclusions:
- Despite Fgf2 upregulation, SES failed to provide photoreceptor neuroprotection in mer(kd) mice.
- Mer(kd) mice displayed inner retinal dysfunction, unlike RCS rats, which may hinder SES efficacy.
- The accelerated degeneration and inner retinal dysfunction in mer(kd) mice might create a retinal environment unresponsive to SES-mediated neuroprotection.
