Bright light vision mediated by human macular cones
Funding: R01 from NIH/NEI, Pigment regeneration mechanisms in the human retina, 2020 - 2025
Related publications:
Functional diversity of human intrinsically photosensitive retinal ganglion cells. Mure, Vinberg, et al. 2019 in Science.
Revival of light-evoked neuronal signals in the post-mortem mouse and human retina. Abbas, Becker, Jones, Mure, Panda, Hanneken and Vinberg, 2020 in bioRxiv.
Revival of light signalling in the postmortem mouse and human retina, Abbas, Becker, Jones, Mure, Panda, Hanneken and Vinberg 2020 in Nature.
Problem/question: Our central retina, fovea and macula, is bombarded by intense flux of photons throughout our lives. In bright light it is expected that almost every pigment in each individual cone is bleached each second. Thus, to escape saturation, the central cones need to regenerate their pigment using mechanisms that are fast and have high capacity. Recent work, in animal models, has revealed cone-specific pigment regeneration pathways that can function either in darkness or require blue light. However, the contribution of these pathways to human vision is not known. Our objective is to resolve the contribution of different visual pigment regeneration pathways in the human macula to our ability to see in bright light or adapt quickly to large and rapid decreases in ambient light.
Approach: We have electrophysiology setups in Salt Lake City and in San Diego where we have established access and protocols, in collaboration with eye banks and Dr. Anne Hanneken (The Scripps Research Institute) to obtain human eyes enucleated from donors within 0.5 – 3 hours postmortem. We have shown that we can study light-evoked function of photoreceptors and ganglion cells in the central (macula) and peripheral human retina. We are using these tissues in electrophysiology, immunostaining, EM and molecular biology experiments to understand the mechanisms that enable vision mediated by human macular cones in very bright quickly changing light environments.
Dark adaptation mechanisms of macular photoreceptors in Age-Related Macular Degeneration
Funding: Research to Prevent Blindness Career Development Award, 2020 – 2024
Problem: As we age and specifically in AMD our ability to adapt to rapid decreases in ambient light is one of the first symptoms that can be observed by patients who, for instance, often have trouble driving at night when ambient light can change quickly (e.g. headlights from oncoming cars). Although research has shown that there seems to be a specific problem with rod dark adaptation potentially due to drusen deposits between RPE and the retina in early AMD, the reason for vision problems during everyday life must originate from compromised signaling of the macular cones. The mechanism for the slower ability of macular cones to dark adapt in AMD or aging is not known. As our R01-funded project is focused on understanding the contribution of different pigment regeneration pathways to macular vision, this RPB project will elucidate how these mechanisms are affected in AMD.
Approach: This project relies on the same approaches as described above but comparing functional, structural and molecular differences between para- and perifoveal rods and cones between healthy and AMD-affected donors. In addition, we are planning to conduct a study with human patients to test, by using psychophysical methods, the role of blue light-dependent pigment regeneration mechanisms in human central vision as well as how it may be affected in AMD.