Purpose: Iron-induced oxidative stress may exacerbate age-related macular degeneration (AMD). We tested the hypothesis the Deferiprone (DFP), as an iron chelator, would attenuate light damage in the mouse retina. To evaluated retinal microglia and complement deposition in light-induced photoreceptor degeneration model.
Methods: A/J mice were treated with or without DFP in drinking water, and then were placed in constant light (2000 lux) for 20 hours. Retinas were evaluated at different times after light exposure. The markers of stress, Heme-oxygenase 1 (HMOX1) and Ceruloplasmin (Cp) were quantified by RT-qPCR. Retinal degeneration was assessed by histology, electroretinography and inflammation at 2 days and 10 days after exposure to damaging white light. Cryosections were antibody stained for a microglia marker (Iba1), C3a receport 1 (c3ar1) and C3.
Results: Light exposure resulted in substantial photoreceptor-specific cell death and RPE loss in control retinas. Dosing with DFP attenuated histopathological alterations in all experimental groups and decreased complement deposition in the outer retina. Robust microglia activation and migration to the outer retina occurred rapidly and DFP treatment also abolished microglia invasion. Bright light-induced reductions in photoreceptor function were significantly ameliorated in DFP treated mice.
Conclusions: The complement system was markedly activated, with substantial complement deposition in the outer retina after light exposure. The light-induced model may be useful in the evaluation of complement inhibitors as well as other neuroprotectants intended for ocular use. DFP is protective against light exposure and has the potential to become an important drug to prevent light-induced stress in the retina.