Thompson, Dorothy A. and Feather, Sally and Stanescu, Horia C. and Freudenthal, Bernard and Zdebik, Anselm A. and Warth, Richard and Ognjanovic, Milos and Hulton, Sally A. and Wassmer, Evangeline and van't Hoff, William and Russell-Eggitt, Isabelle and Dobbie, Angus and Sheridan, Eamonn and Kleta, Robert and Bockenhauer, Detlef (2011) Altered electroretinograms in patients with KCNJ10 mutations and EAST syndrome. JOURNAL OF PHYSIOLOGY-LONDON, 589 (7). pp. 1681-1689. ISSN 0022-3751, 1469-7793
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Non-technical summary Light stimulates ion flow through the retina. This generates a potential change at the cornea which is recorded as an electroretinogram (ERG). Our understanding of the role of potassium ions in generating the ERG is based on animal models. The KCJN10 gene constitutes Kir4.1, the principle potassium channel expressed on the retinal Muller cell. We have been able to study the impact of this potassium channel on the human retina for the first time by recording the ERGs of patients with EAST syndrome who have known mutations of KCJN10. Our data show a reduction in the amplitude of the photopic negative response of the light-adapted ERG and a decrease in the sensitivity of the dark-adapted ERG. These data increase our understanding of how the ERG is generated and why these ERG parameters may be affected in disease.The K+ channel expressed by the KCNJ10 gene (Kir4.1) has previously demonstrated importance in retinal function in animal experiments. Recently, mutations in KCNJ10 were recognised as pathogenic in man, causing a constellation of symptoms, including epilepsy, ataxia, sensorineural deafness and a renal tubulopathy designated as EAST syndrome. We have studied the impact of KCNJ10 mutations on the human electroretinogram (ERG) in four unrelated patients with EAST syndrome. Corneal ganzfeld ERGs were elicited in response to flash stimuli of strengths of 0.001-10 phot cd s/m2 presented scotopically, and 0.3-10 phot cd s/m2 presented photopically. ERG waveforms from light-adapted retinae of all patients showed reduced amplitudes of the photopic negative response (PhNR) (P < 0.001). The photopic ERGs showed a delay in b-wave time to peak, but the photopic hill, i.e. the relative variation of time to peak and amplitude with luminance flash strength, was preserved. Scotopic ERGs to flash strengths 0.01 to 0.1 phot cd s/m2 showed a delay of up to 20 ms before the onset of the b-wave in two patients compared to controls. Stimulus-response functions were fitted by Michaelis-Menten equations and showed significantly lower retinal sensitivity in two patients than in controls (P < 0.001). Our study for the first time in the human ERG shows changes in association with KCNJ10 mutations affecting a Muller cell K+ channel. These data illustrate the role of KCNJ10 function in the physiology of proximal and possibly also the distal human retina.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RECTIFYING POTASSIUM CHANNEL; LIGHT-EVOKED CHANGES; RETINAL GLIAL-CELLS; SENSORINEURAL DEAFNESS; MULLER CELL; OSCILLATORY POTENTIALS; EXPERIMENTAL GLAUCOMA; NEGATIVE RESPONSE; CAT RETINA; MEMBRANE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Richard Warth |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Jun 2020 07:01 |
| Last Modified: | 23 Jun 2020 07:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21058 |
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