Abstract
Purpose :
Ephrin (Eph) receptors serve as crucial environmental sensors in cell signaling pathways. In the central nervous system (CNS), Eph receptors play key roles in development, morphogenesis, and regeneration. These receptors are also associated with patterning of the visual system, axon guidance, and synaptogenesis in the retina. Of the 14 members of the Eph receptor family, the Epha10 receptor specifically is highly expressed in S-cone-like photoreceptors in the mouse retina, though its function remains unknown. To elucidate Epha10 function, we decided to examine its expression, perform a comprehensive behavioral phenotyping and assessments of the brain and retina morphologies of the Epha10-KO mouse, and evaluate how loss of Epha10 impacts molecular characteristics of retina and brain.
Methods :
Control C57BL6 (WT) and Epha10-KO mice of various ages are being used in this study. Open field testing is performed to establish behavioral profiles for both WT and KO animals. Optomotor testing is conducted to assess visual function by determining visual acuity (VA) and contrast sensitivity thresholds. Retina function is evaluated via electroretinographic recordings (ERG). The structure and morphology of both the brain and retina are being examined via immunostaining and immunohistochemistry. Transcriptomic analyses are being utilized to investigate the CNS pathways in which the Epha10 receptor plays a functional role.
Results :
Optomotor results were not indicative of significant changes in VA between 24-month WT and KO females as both had an average VA of 0.35 cycles/degrees (c/d). WT males of the same age exhibited a higher average acuity of 0.4 c/d while KO males had an average VA of 0.37 c/d. However, the scotopic a-wave, b-wave, and photopic b-wave ERG results exhibited greater amplitudes in 24-month KO males and females in comparison to WTs. We are currently performing expression and RNA-seq analyses.
Conclusions :
Our results indicate that the Epha10 receptor might have distinct functions within the visual systems of male and female mice. Further studies are being pursued to investigate Epha10 and its ligand’s possible role in promoting photoreceptor survival and maintaining homeostasis in healthy and diseased state CNS models.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.