MMPC :: MICROMouse Program Application Abstract

MICROMouse Program Application Abstract

MMPC Funded Abstracts

MICROMouse

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MRI Phenotyping of Murine Diabetic Retinopathy

Bruce Berkowitz (Detroit, MI)

MICROMouse Program

This new proposal is a continuation of our previous MMPC P&F that was focused on the utility of manganese-enhanced MRI (MEMRI) to non-invasively phenotype retinal function based on the extent of layer-specific accumulation of Mn2+ ion. The goal of our new proposal is to elucidate how central retina function and visual performance become impaired during the clinically silent stages of diabetic retinopathy. Normal vision requires good central retina function including light and dark adaptation and processing of visual information. If adaptation is persistently impaired (i.e., dysadaptation) neurodegeneration and vision loss will ultimately occur. On MEMRI examination, we find that diabetic, dark adapted rodents have a light adapted phenotype and subnormal visual processing in post-receptor retina before microvascular lesions are apparent; visual performance was also impaired on optokinetic tracking (OKT) assessment. During this grant period we will focus on two potential diabetes-induced mechanisms of retinal dysadaptation: subnormal levels of 11-cis-retinal (the key light-sensing chromophore) and supernormal polyamine content. Our overriding hypothesis is that hyperglycemia causes reductions in 11-cis-retinal and / or increases in retinal polyamines, and that these changes can fully explain the extent of retinal dysadaptation and impaired visual performance observed in early experimental diabetic retinopathy with MEMRI and OKT. Aim: Test that diabetes-induced retinal dysadaptation and impaired visual performance are due to reduced 11-cis-retinal levels and / or increased polyamine levels. These experiments will identify the combination of treatments that best normalize intraretinal dysadaptation and visual performance. The proposed experiments are expected to help elucidate mechanisms by which diabetes produces retinal dysadaptation and vision loss. If successful, a future grant proposal is envisioned that will investigate chronically treated animals as a potential new approach to reduce and / or prevent sight-threatening complications of this disease. This application is responsive to the Pilot & Feasibility Program part of the MICROMouse Program.

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