A groundbreaking study led by biomedical scientist Aleksander Tworak has opened new doors in understanding how our eyes adjust to varying light conditions. His research, focusing on the RGR-dependent visual pigment recycling process, marks a significant advance in the study of mammalian vision.
Dr. Aleksander Tworak, a distinguished figure in the field of ophthalmology research, currently serves as a project scientist at the University of California Irvine (UCI) Gavin Herbert Eye Institute. In this role, he continues his vital work in the renowned lab of Dr. Palczewski, focusing on the intricate biology and various diseases affecting the retina and retinal pigment epithelium. His research is instrumental in unraveling the complex mechanisms of visual function and its disorders.
Alongside his role at UCI, Dr. Tworak holds the position of principal investigator on an individual grant from the Knights Templar Eye Foundation, a testament to his expertise and dedication to advancing ophthalmological knowledge. His academic journey, marked by a strong foundation in biochemistry, culminated in a Doctor of Philosophy from the prestigious Institute of Bioorganic Chemistry at the Polish Academy of Sciences. Dr. Tworak's extensive research and academic background in biochemistry enrich his contributions to the field, making him a vital asset to ongoing studies and developments in retinal health and disease.
When he was starting out as a postdoctoral scholar, Dr. Tworak—alongside a team of ophthalmic scientists—got intrigued by the mechanisms of visual pigment regeneration, particularly under daylight conditions where the demand for visual chromophores remains the highest. This led him to discover that the retinal G-protein-coupled receptor (RGR), an enzyme expressed in the retinal pigment epithelium (RPE) and Müller cells, very efficiently produces 11-cis-retinal from its all-trans isomer upon illumination with a narrow band of green light. The results published in the Journal of Biological Chemistry in 2019 for the first time proved the capability of RGR photoisomerase to contribute to visual pigment regeneration significantly.
While this study became highly read, cited, and recognized by many world-renowned professional organizations, including The Association for Research in Vision and Ophthalmology (ARVO), two big questions still remained unanswered: what is the individual contribution of the two RGR pools (in the RPE and Müller glia) to the visual pigment regeneration. Whether together, they are capable of supplying enough 11-cis-retinal to meet the demand of cones, even under the brightest light conditions.
Dr. Tworak's most recent research published in Cell Reports provides the answers. Using a unique cell-specific gene reactivation approach and electroretinographic measurements in mice, Tworak and his team reveal the integral roles of the RPE and Müller glia in supporting both scotopic (low-light) and photopic (bright-light) vision. Dr. Tworak's experiments show that RGR aids in continuous vision in daylight conditions and under a sharp switch to a dimmer environment.
Improving Understanding of the Visual Cycle
The novelty of Dr. Tworak's research lies in the ability to precisely explore how different cellular components contribute to visual pigment recycling. Prior to this study, the specific contributions of RPE and Müller glia to visual pigment regeneration were unclear. By isolating the RGR function in each cell type, Tworak's team has been able to demonstrate the critical role played by both cell types in supporting visual function.
Furthermore, the study provides insight into the biochemical processes behind visual pigment regeneration. It reveals that 11-cis-retinal formed through RGR-mediated photoisomerization is produced rapidly, matching the high demand for chromophore under daylight conditions. The speed outpaces the hydrolytic release of all-trans-retinal from rod opsin, proving that RGR activity closes the gap between the chromophore demand and supply in intense daylight.
Overall, Dr. Tworak's research presents a significant stride forward in understanding the visual cycle. Historically, the RPE-based classical cycle was identified as the major path for trans-cis retinoid isomerization. However, its pace falls short of meeting the chromophore demand of cones in bright light, and the origin of the additional supply remains unclear. The study identifies the RGR-dependent photic visual cycle as an essential alternative.
What's next?
Since starting his scientific career, Dr. Tworak has always been interested in research relevant to human health and wellbeing. The opportunity to pursue his passion in the field of ophthalmic research offered him a chance to help millions of people worldwide who are affected by blinding disorders. "This is a chance I don't want to miss," says Dr. Tworak. "I'm amazed by how the energy of light is utilized in our eye in a dual way: to activate the visual pigment and to regenerate it to support uninterrupted vision. And I want to see whether we could use this process to help prevent vision loss in patients with disruptions in the classical visual cycle."
