Preclinical Analysis Of The Iron-Binding Drugs SIH And BSIH For AMD
The goal of this proposal is to determine whether the iron binding drugs SIH and BSIH, which are very effective in protecting cultured retinal cells, will be similarly protective in living animals. To this end, we will test the drugs in our Cp/Heph iron overload-induced model of AMD, which is a mouse that possesses a number of eye features in common with human AMD.
Potential benefit for AMD patients: This line of research represents a novel therapeutic area for AMD. Patients with AMD have elevated retinal iron levels, which may increase oxidative damage. We have found recently that the cell-permeable iron binding drugs SIH and BSIH protect cultured retinal cells against oxidant induced cell death. We now propose to test SIH and BSIH for their ability to decrease retinal iron overload and protect against retinal degeneration in our Cp/Heph double gene knockout mouse model.
Specific Aim1: To determine whether SIH and BSIH can decrease retinal iron levels when administered systemically or by eye drops in mice.
Specific Aim2: To determine whether SIH and BSIH will protect the Cp/Heph mice from retinal degeneration.
If SIH and/or BSIH prove non-toxic and effective for prevention of retinal degeneration, this will provide proof-of-principle for the possibility that SIH or similar iron binding drugs could, after further testing, be used to reduce the risk of vision loss in patients with early AMD.