Diabetic Retinopathy (DR) is a major cause of visual dysfunction, yet much remains unknown regarding the specific molecular events that contribute to diabetes-induced retinal pathophysiology. Herein, we review the impact of oxidative stress on DR, and explore evidence that supports a key role for the stress response protein regulated in development and DNA damage (REDD1) in the development of diabetes-induced oxidative stress and functional defects in vision. It is well established that REDD1 mediates the cellular response to a number of diverse stressors through repression of the central metabolic regulator known as mechanistic target of rapamycin complex 1 (mTORC1). A growing body of evidence also supports that REDD1 acts independent of mTORC1 to promote oxidative stress by both enhancing the production of reactive oxygen species and suppressing the antioxidant response. Collectively, there is strong preclinical data to support a key role for REDD1 in the development and progression of retinal complications caused by diabetes. Furthermore, early proof-of-concept clinical trials have found a degree of success in combating ischemic retinal disease through intravitreal delivery of an siRNA targeting the REDD1 mRNA. Overall, REDD1-associated signaling represents an intriguing target for novel clinical therapies that go beyond addressing the symptoms of diabetes by targeting the underlying molecular mechanisms that contribute to DR.
|Original language||English (US)|
|Number of pages||10|
|Journal||Free Radical Biology and Medicine|
|State||Published - Mar 2021|
All Science Journal Classification (ASJC) codes
- Physiology (medical)