About Our Research
The Vinberg Laboratory at the John A. Moran Eye Center at the University of Utah is using the latest technology and experimental approaches to understand how light signaling in the retina is affected in age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa. This understanding is critical for developing new treatments to cure or slow visual impairment and blindness.
Current Projects
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 AMD
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.
Modulation of Light Signaling in the Retina during Retinal Degenerative Disease
Funding
Functional plasticity in retinal degenerative disease, R01, NEI, 2023-2028
Problem/Question
Many blinding diseases are initially caused by photoreceptor degeneration and various strategies are being developed to restore vision (e.g. using stem cell and gene therapy approaches). However, it is now well-known that photoreceptor degeneration triggers a remodeling process of the inner-retina that may corrupt retinal signaling and make these therapies ineffective.
Although a lot is known about the remodeling process at structural level, it has been harder to assess how it affects light signaling and vision. We ask questions about remodeling: Is it good or bad to light signaling in the retina? Does it promote or slow-down vision loss? How is light signaling changing at the level of bipolar and ganglion cells during photoreceptor degeneration? What are the molecular mechanisms underlying the functional changes in the inner retina?
Approach
We are studying a well-established animal model of retinitis pigmentosa (P23H rhodopsin knock-in mouse), together with ability to silence cones and/or rods to probe how light signaling in the inner retina is affected during rod photoreceptor degeneration. Light signaling is studied using ex vivo ERG, patch clamp retinal slice recordings from bipolar cells, and large scale MEA recordings from ganglion cells. These approaches are combined with bulk and single cell RNA sequencing analysis, together with immunostaining and high-resolution confocal microscopy and EM analysis of the synaptic ultrastructures.
Related publications
- UCI Ophthalmology Seminar Series Talk
- Homeostatic plasticity in the retina is associated with maintenance of night vision during retinal degenerative disease. Leinonen, Pham, Boyd, Santoso, Palczewski and Vinberg, 2020 in eLife
In the News
- Science Daily
How night vision is maintained during retinal degenerative disease - New findings in mice could inform novel treatment strategies for diseases that cause blindness
- NEI News
How is night vision maintained during retinal disease? - NEI-funded research suggests that second-order neurons in the retina play a role in preserving night vision
- Moran Eye Center Newsletter
How is Night Vision Maintained during Retinal Disease? - New research provides insight on how people with retinal degenerative disease can maintain their night vision for a relatively long period of time.
Oxygen and Light Signaling in Healthy and Diabetic Photoreceptors
Funding
University of Utah Seed Grant and Diabetes Research Connection grants to Dr. Silke Becker.
Related Publications
- Rod phototransduction and light signal transmission during type 2 diabetes. Becker, Carroll and Vinberg, 2020, BMJ Open Diabetes Res Care
- Diabetic photoreceptors: Mechanisms underlying changes in structure and function. Becker, Carroll and Vinberg, 2020, Visual Neuroscience
Problem/Question
Diabetic retinopathy is one of the main complications in patients with diabetes and the most common reason for blindness in the working-age population in the USA. Traditionally, diabetic retinopathy has been diagnosed by changes to retinal blood vessels. Recently, it has been discovered, however, that the function of photoreceptors is actually disrupted before these vascular changes occur and it is possible that this may drive the development of diabetic retinopathy. In this project, we try to understand why and how photoreceptors are affected this early in the disease.
Hypoxia (or lack of oxygen) is one of the main factors driving retinal disease in diabetes. We study whether this is also the reason why photoreceptors function poorly in the diabetic retina and how it affects other cells in the retina. Understanding the early pathological changes in diabetic retinopathy may help us develop ways to diagnose and treat the disease early before clinical damage has occurred.
Approach
We use mice that develop diabetes, which allows us to mimic changes by diabetes in the human retina. By combining in vivo and ex vivo ERG, we can distinguish between functional changes that are caused by direct damage to photoreceptors versus systemic effects that indirectly affect the retina.
Ex vivo ERG also allows us to alter the environment that the retina is exposed to and thus mimic changes in the diabetic animal. We use this approach to change the oxygen concentration that the retina is exposed to, and monitor changes in the function of retinal cells. These studies are also accompanied by experiments from donated human eyes from healthy and diabetic donors.
About Dr. Vinberg
Frans Vinberg, PhD, obtained his MSc degree in Engineering Physics and PhD degree in Biomedical Engineering from Aalto University, Finland. In Finland, he studied ionic mechanisms in mammalian photoreceptors by using electrophysiology and pharmacology tools. Dr. Vinberg obtained his postdoctoral training under Vladimir Kefalov, PhD, at Washington University in St. Louis between 2012 and 2017. There, his main focus was to study the role of Ca2+ homeostasis in the photoreceptor function and long-term survival by using a wide range of electrophysiology, genetics, pharmacology and molecular biology tools.
During his time at WashU, Dr. Vinberg developed a device that allows researchers to use human donor retinas to assess the function of retinal cells and the effects of drugs on them. The Ex Vivo ERG is commercially available and spreading around the world, facilitating our understanding about retinal signaling and blinding diseases.
Dr. Vinberg joined the University of Utah Department of Ophthalmology and Visual Sciences as assistant professor in August 2017. He's also a member of the University’s Neuroscience program. Dr. Vinberg is passionate about science, Formula 1, ice hockey and enjoys skiing as well as other outdoor sports.
