Abstract
Purpose :
Retinoschisin-1 (RS1) protein is expressed in photoreceptors and bipolar cells and has a role in retinal cell adhesion. Mutations in the RS1 gene lead to X-linked retinoschisis (XLRS) in males and is in the focus of novel genetic therapies. The aim of this study is to investigate the pathophysiology of the retina in XLRS with electroretinogram (ERG) in response to heterochromatic stimulation at two different temporal frequencies aiming to emphasize cone-opponent and luminance responses.
Methods :
Male patients and female carriers with genetically confirmed mutations in RS1 gene were included. ERGs were recorded, either preferentially activating the (red–green) opponent or the luminance pathway, and data from of XLRS patients (n=5) and carriers (n=5) were compared to normal male controls (n=10). The stimuli were heterochromatic sinusoidal modulations (HFM) at a mean luminance of 200 cd/m2. Three steps were measured with different red to green ratios for both 12 and 36 Hz. Furthermore, light-adapted ON and OFF responses were recorded using the sawtooth modulation.
Results :
XLRS female carriers (mean age 46±6.8 years, range 39 to 54 years), and age-matched controls showed comparable HFM ERGs at both 12 and 36 Hz. XLRS male patients (mean age 24±3.3 years, range 20-28 years), on the other hand, showed lower responses at 36 Hz (F(2,35) = 9.928 and p < 0.001). Interestingly, the 12 Hz HFM pattern for the XLRS patients was consistent with a "luminance profile," rather than the “opponent profile” observed in the control and carrier groups. The "luminance profile" is normally observed at 36 Hz and is associated with the magnocellular pathway, whereas the “opponent profile” is normally observed at 12 Hz and is associated with the parvocellular pathway. We observed a greater deficit in the ON response than in the OFF response of the cone system in XLRS patients, as expected, but no significant differences between carriers and normal controls.
Conclusions :
The absence of retinoschisin-1 is likely to disturb cone-opponent processing in XLRS patients. We hypothesize that asymmetric ON/OFF signals may hinder cone-opponent cells to be activated at 12 Hz. HFM protocols could be an objective and useful measure for natural history and therapeutic studies in XLRS.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.