Metabolic stress in the form of hypoglycemia has deleterious effects on vision. My colleagues and I have found age-related losses of retinal and visual function in mice rendered hypoglycemic from a null mutation in the glucagon receptor gene, Gcgr. I hope to gain insight into the underlying mechanisms of this vision loss by attempting to modulate its time course in Gcgr -/- mice. I will attempt to delay and rescue the effects of chronic hypoglycemia on vision by examining various durations and timings of high carbohydrate diet and gene therapy treatment. Retinal function will be quantified via electroretinogram (ERG), visual function will be assessed using a novel optomotor behavioral technique (Optomotry? ) and retinal anatomy will be visualized using standard anatomical methods. This project has two aims:
Aim 1 : Attempt dietary rescue of retinal and visual function of metabolically stressed mice.
Aim 2 : Attempt rescue of retinal and visual function of metabolically stressed mice using gene therapy. Specific experiments will determine if there is a critical duration and/or timing of high carbohydrate diet or gene therapy treatment that will delay vision loss or restore vision in Gcgr-/- mice. Potential medical benefits include : (1) Identification of a metabolic stress factor in retinal and visual function (2) Use of innovative methods for measures of the retinal and visual function (3) Possible insights into causes of human late-onset retinal degeneration (4) Possible identification of a novel gene therapy for vision loss caused by metabolic stress
