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.
In another research focus, the lab garnered international attention in 2022 when it published methods for preserving and conducting testing on functioning human retinal tissue, part of a series of discoveries that stand to transform brain and vision research. The lab is part of a new national effort aiming for the first-ever transplant of human eyes to reestablish sight.
Current Projects
Making Sight-Restoring Whole Eye Transplants a Reality
Funding
The Transplantation of Human Eye Allografts (THEA) program awarded up to $56 million in late-2024 for the six-year Viability, Imaging, Surgical, Immunomodulation, Ocular Preservation and Neuroregeneration (VISION) Strategies for Whole Eye Transplant project. The Vinberg lab is on track to receive close to $1.5 million in direct and indirect funding for the first four years as part of VISION, led by principal investigator Jeffrey Goldberg, MD, PhD, Blumenkranz Smead professor and chair of ophthalmology at the Byers Eye Institute at Stanford University. This research is, in part, funded by the Advanced Research Projects Agency for Health (ARPA-H).
Problem/Question
“Whole eye transplantation has many barriers that must be overcome, one of the largest being that we don’t have a way to regenerate the optic nerve, which carries visual information to the brain,” explains Frans Vinberg, PhD. “Part of our work will be investigating ways to sustain a human donor eye in its entirety, including the retinal neurons that carry light signals to the brain.”
Background
The Vinberg lab has previously identified oxygen deprivation as the critical factor for restoring functional light-sensing tissue from the eye’s retina. Vinberg, who has a PhD in Biomedical Engineering, designed a special transportation unit that restores oxygenation and other nutrients to organ donor eyes. Vinberg also built a device to stimulate the retina and measure the electrical activity of its cells. With this approach, he was able to restore a specific electrical signal seen in living eyes, the “b wave.”
The time may be right for a transplantation breakthrough: scientists can now leverage emerging microsurgical techniques, coupled with genetic and cell-based therapies, in their attempts to preserve or regrow nerves from the eye to the brain.
Related publications
- Restoring and sustaining human postmortem retinal light responses with scalable methods for testing degenerative disease therapies. Becker S, Allen J, Morison ZL, Saeid S, Koskelainen A, Vinberg F. bioRxiv [Preprint]. 2024 Nov 6:2024.11.04.621932.
- Revival of light signalling in the postmortem mouse and human retina. Abbas F, Becker S, Jones BW, Mure LS, Panda S, Hanneken A, Vinberg F. Nature. 2022 Jun;606(7913):351-357.
In the News
- Advanced Research Projects Agency for Health
ARPA-H Announces Pioneering Investments to Restore Vision to People Who are Blind - Investments aim for first-ever transplant of human eyes to reestablish sight.
- Moran Eye Center
Moran Researcher Joins Elite Team Working to Make Human Eye Transplantation Possible - Frans Vinberg, PhD, is part of a project bringing together more than 40 scientists, doctors, and industry experts hand-picked from around the country.
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 the 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 the 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.
Research Publications
- Restoring and sustaining human postmortem retinal light responses with scalable methods for testing degenerative disease therapies. Becker S, Allen J, Morison ZL, Saeid S, Koskelainen A, Vinberg F. bioRxiv [Preprint]. 2024 Nov 6:2024.11.04.621932.
- Closed-perfusion transretinal ERG setup for preclinical drug and nanostructure testing. Saeid S, Pitkanen M, Ilonen E, Niskanen J, Tenhu H, Vinberg F, Koskelainen A. IEEE Trans Biomed Eng. 2024 Nov 7;PP.
- Acyl-CoA synthetase 6 controls rod photoreceptor function and survival by shaping the phospholipid composition of retinal membranes. Wang Y, Becker S, Finkelstein S, Dyka FM, Liu H, Eminhizer M, Hao Y, Brush RS, Spencer WJ, Arshavsky VY, Ash JD, Du J, Agbaga MP, Vinberg F, Ellis JM, Lobanova ES. Commun Biol. 2024 Aug 21;7(1):1027.
- Modeling complex age-related eye disease. Becker S, L'Ecuyer Z, Jones BW, Zouache MA, McDonnell FS, Vinberg F. Prog Retin Eye Res. 2024 May;100:101247.
- Optimizing the Setup and Conditions for Ex Vivo Electroretinogram to Study Retina Function in Small and Large Eyes. Abbas F, Vinberg F, Becker S. J Vis Exp. 2022 Jun 27;(184).
- Revival of light signalling in the postmortem mouse and human retina. Abbas F, Becker S, Jones BW, Mure LS, Panda S, Hanneken A, Vinberg F. Nature. 2022 Jun;606(7913):351-357. doi: 10.1038/s41586-022-04709-x. Epub 2022 May 11. PubMed PMID: 35545677.
- Identification of small-molecule allosteric modulators that act as enhancers/disrupters of rhodopsin oligomerization. Getter T, Kemp A, Vinberg F, Palczewski K. J Biol Chem. 2021 Dec;297(6):101401.
- Transduction and Adaptation Mechanisms in the Cilium or Microvilli of Photoreceptors and Olfactory Receptors From Insects to Humans. Abbas F, Vinberg F. Front Cell Neurosci. 2021;15:662453. doi: 10.3389/fncel.2021.662453. eCollection 2021. Review. PubMed PMID: 33867944; PubMed Central PMCID: PMC8046925.
- Diabetic photoreceptors: Mechanisms underlying changes in structure and function. Becker S, Carroll LS, Vinberg F. Vis Neurosci. 2020 Oct 6;37:E008.
- Homeostatic plasticity in the retina is associated with maintenance of night vision during retinal degenerative disease. Leinonen H, Pham NC, Boyd T, Santoso J, Palczewski K, Vinberg F. Elife. 2020 Sep 22;9.
- Rod phototransduction and light signal transmission during type 2 diabetes. Becker S, Carroll LS, Vinberg F. BMJ Open Diabetes Res Care. 2020 Aug;8(1).
- Increasing Ca2+ in photoreceptor mitochondria alters metabolites, accelerates photoresponse recovery, and reveals adaptations to mitochondrial stress. Hutto RA, Bisbach CM, Abbas F, Brock DC, Cleghorn WM, Parker ED, Bauer BH, Ge W, Vinberg F, Hurley JB, Brockerhoff SE. Cell Death Differ. 2020 Mar;27(3):1067-1085.
- Functional diversity of human intrinsically photosensitive retinal ganglion cells. Mure LS, Vinberg F, Hanneken A, Panda S. Science. 2019 Dec 6;366(6470):1251-1255.
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.
