Progressive Alterations of the Human Retinal Proteome by Diabetes and Diabetic Retinopathy
Abstract
Diabetes is a continuously growing health burden worldwide and in the United States, for the general population as well as the Service members, Veterans, and their beneficiaries, and as such it is listed as one of the Fiscal Year 2019 Topic Area of the Peer Reviewed Medical Research Program. Among the major complications associated with diabetes, diabetic retinopathy is the primary ocular complication and represents the primary cause of loss of vision in the working- and military-age population. While recent progress have been made relative to the treatment of late stages of the disease, there remains a dire need for additional treatment options, especially relative to early intervention to prevent or slow down the progression of retinal nerve cell damage and subsequent vision impairment. The limited progress relative to these aspects of the disease is in a great part due to the fact that most of the current knowledge relative to diabetes and diabetic retinopathy comes from animal models that do not fully recapitulate the human normal and disease physiology. While animal models of diabetes have been and continue to be very useful to study specific aspects of the disease mechanisms and test novel therapeutic targets preclinically, they have shown their limitations when not complemented by human studies as demonstrated by the repeated failures of clinical trials assessing targets not previously validated in humans. This application specifically tackles this ongoing lack of information by assessing the diabetes and diabetic retinopathy-associated changes affecting the protein profile of the retina and the vitreous humor as a function of the onset and progression of the disease. Information about the protein profile of the retina under such circumstances will be critical to improve our overall understanding of the disease mechanisms and identify or validate potential therapeutic targets for the prevention and treatment of diabetic retinopathy. Additionally, determination of the protein profile of the vitreous humor as a function of the disease stages is capital to identify and develop biomarkers of the progression of the disease. Indeed, while it is impossible to do so for the retina, it is possible to biopsy the vitreous fluid from human patients and thus increased knowledge of the correlation between the vitreous proteome and diabetic retinopathy progression will give us invaluable insights for the identification of such markers of progression. Taken together, the research described in this application will play a key role in improving diagnostic and treatment of diabetic patients for the prevention and therapeutic intervention of diabetic retinopathy.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010155
Entities
People
- Patrice E. Fort
Organizations
- United States Army
- University of Michigan