Regulatory mechanisms of the protective function of alphaA- & alphaB-crystallins in retinal neurons and glia

• Applicant: Dr. Anne Rübsam
• Subject Area: Ophthalmology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2016 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 326938900

Still today Diabetic retinopathy (DR) accounts for the most common reason blindness in industrial nations with a further increasing rate. Since the last decade there is a rethinking regarding the pathophysiology of the disease; away from the vasculature changes of the late stages of DR towards the early changes in the neurons and their supporting glial cells. Hence there is a new perspective regarding the therapeutic approaches in the treatment of DR. Recently Fort et al. in Ann Arbor, Michigan revealed that a family of proteins, the alpha--crystallins are highly upregulated in animal models of type 1 and 2 diabetes. Immunoreactivity for alpha-crystallin increases in the retinas of patients with diabetes, confirming that the changes observed in animal models are relevant to the human pathology alpha-Crystallins protect retinal cells (neurons and Müller glial cells) from acute stress-induced cell death; however, in chronic diabetes the protective properties of crystallins are altered and retinal cell death still occurs. Analysis of retinal lysates from diabetic animals shows post-translational modifications of the crystallin proteins, although the exact nature and functional consequences of these post-translational modifications are currently unknown. A better understanding of the biochemical changes to crystallin proteins caused by chronic diabetes, the exact function of cyrstallin proteins in the retina during diabetes and how these changes affect the protective functions of crystallin proteins would expand our knowledge of the innate neuroprotective mechanisms in the retina and provide a necessary first step toward manipulating or optimizing the function of neuroprotective proteins in retinal diseases. The long-term goal of this research is to determine how the protective functions of alpha-crystallins can be manipulated to preserve vision in patients with diabetes. The objective of this project is to identify mechanisms by which diabetes modulates the function of alphaA- and alphaB-crystallin proteins in retinal cells and how these mechanisms are modified during diabetes.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Patrice Fort