ON than OFF pathway disruption leads to greater deficits in visual function and retinal dopamine signaling

• Type of Material: Article
• Authors: Moe H Aung, Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Dr, Atlanta, GA 30332, United States; Kelleigh Hogan, Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Dr, Atlanta, GA 30332, United States; Reece E Mazade, Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Dr, Atlanta, GA 30332, United States; Han na Park, Emory University; Curran S Sidhu, Emory University; Paul Iuvone, Emory University; Machelle Pardue, Emory University
• Language: English
• Date: 2022-05-03
• Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Elsevier Ltd
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.exer.2022.109091
• Title of Journal or Parent Work: EXPERIMENTAL EYE RESEARCH
• Volume: 220
• Start Page: 109091
• End Page: 109091
• Grant/Funding Information: This project was supported by the National Institutes of Health [NIH R01 EY016435 (MTP), NIH R01 EY004864 and NIH R01 EY027711 (PMI), NIH P30 EY006360], Department of Veterans Affairs [Rehabilitation R&D Service Research Career Scientist Award IK6 RX003134 (MTP)], and Research to Prevent Blindness [Departmental Award]. The funding organizations had no role in the design or conducting of this research.
• Keywords: Vsx1(--/-); GENE; IDENTIFICATION; VISION; BIPOLAR CELLS; -Dopamine; DOPAC; ELECTRORETINOGRAM; Nob; SELECTIVE GANGLION-CELLS; RESPONSES; Life Sciences & Biomedicine; DIFFERENTIATION; OPTOKINETIC NYSTAGMUS; Science & Technology; Optomotor response (OMR); Ophthalmology; MOUSE MODEL
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

The visual system uses ON and OFF pathways to signal luminance increments and decrements. Increasing evidence suggests that ON and OFF pathways have different signaling properties and serve specialized visual functions. However, it is still unclear the contribution of ON and OFF pathways to visual behavior. Therefore, we examined the effects on optomotor response and the retinal dopamine system in nob mice with ON pathway dysfunction and Vsx1−/− mice with partial OFF pathway dysfunction. Spatial frequency and contrast sensitivity thresholds were determined, and values were compared to age-matched wild-type controls. Retinas were collected immediately after visual testing to measure levels of dopamine and its metabolite, DOPAC. At 4 weeks of age, we found that nob mice had significantly reduced spatial frequency (19%) and contrast sensitivity (60%) thresholds compared to wild-type mice. Vsx1−/− mice also exhibited reductions in optomotor responses (3% in spatial frequency; 18% in contrast sensitivity) at 4 weeks, although these changes were significantly smaller than those found in nob mice. Furthermore, nob mice had significantly lower DOPAC levels (53%) and dopamine turnover (41%) compared to controls while Vsx1−/− mice displayed a transient increase in DOPAC levels at 4 weeks of age (55%). Our results show that dysfunction of ON pathways leads to reductions in contrast sensitivity, spatial frequency threshold, and retinal dopamine turnover whereas partial loss of the OFF pathway has minimal effect. We conclude that ON pathways play a critical role in visual reflexes and retinal dopamine signaling, highlighting a potential association for future investigations.