Maria Grant, M.D., professor and Eivor and Alston Callahan, M.D., Endowed Chair in the Department of Ophthalmology and Visual Sciences at the University of Alabama at Birmingham, has been awarded a four-year, $2.67 million R01 grant from the National Institute of Health (NIH) to continue research combining her dual expertise in endocrinology and ophthalmology.
Recently published by Gut BMJ as a journal and video abstract, Grant’s research revealed that bacterial metabolites from the gut have protective effects on the retina—a groundbreaking discovery identified for the first time by her team.
This key metabolite, idole-3-proprionic acid (IPA), is produced when bacteria within the gut break down tryptophan, an essential amino acid that supports healthy gut function.
Individuals with Type 2 diabetes are unable to absorb tryptophan effectively. As a result, they do not benefit from the protective benefits of IPA and are more prone to diabetic retinopathy, a condition that damages blood vessels in the retina and could lead to vision loss.
With a team of collaborators, Grant will continue her cross-disciplinary work with three goals in mind:
Optimize tryptophan production from IPA
Grant and her collaborators have already identified the benefits of IPA on the retina. The next step is to optimize tryptophan production by developing genetically modified probiotic bacteria that can express the necessary enzymes to make IPA. Her team will also identify other methods, including tryptophan-containing dipeptides, which supplement and promote the growth of tryptophan-producing bacteria and optimize IPA production in the gut.
Create eye injection treatment from derived metabolites
Grant’s team, in collaboration with Qingguo Xu, D.Phil., professor in the Department of Pharmaceutics at Virginia Commonwealth University, are developing slow-release microparticles that release IPA over time. This novel treatment will be given through an eye injection to maximize benefits on the retina. Through this treatment, Grant aims to stop the progression of diabetic retinopathy and decrease the risk of permanent vision loss associated with the disease.
Study how the metabolites function
While Grant’s research supports IPA treatment for diabetic retinopathy, researchers do not fully understand how this metabolite supports the retina. This third objective will focus on characterizing and studying the Pregnane X Receptor (PXR), a protective, inflammation-regulating bridge between the gut microbiome and the eyes. Known as a defense mechanism against foreign toxins, Grant’s project will assess how the PXR interprets and interacts with IPA—opening the door for countless clinical and sight-saving implications.
Grant’s background is rooted in endocrinology, but she took interest in studying the retina and completed her research fellowship at the Wilmer Eye Institute at Johns Hopkins University. With more than 40 years of experience in ophthalmic and retinal research, she never lost interest in systemic biology.
“We contain an auxiliary genome within us, the gut microbiome, that helps us in ways we only partially understand,” Grant said. “The survival of microbes and the host is co-dependent. Our research explores mechanisms that can beneficially impact general health and potential treatments for diabetic retinopathy.”
Grant and the Department of Ophthalmology and Visual Sciences will lead this four-year R01 in collaboration with co-principal investigators Michael E. Boulton, Ph.D., professor at UAB Ophthalmology; and Qiuhong Li, Ph.D., associate professor at the University of Florida.