Purpose
to study the protective effect of heme-oxygenase-1 (HO-1) in a mice model of atrophic age-related macular degeneration (AMD) by gene therapy
Methods
Two-month-old C57BL/6J mice were received subretinal injection of AAV-HO-1 or AAV-LacZ. Three weeks later, mice were immunized by peritoneal injection of carboxyethylpyrrole-mouse serum albumin (CEP-MSA) in complete Freund’s adjuvant (CFA) at day 0, followed by challenge with CEP-MSA in incomplete Freund’s adjuvant (IFA) at day 10, and challenged with CEP-MSA in CFA at 10 days before sacrifice. Three months after immunization, the mice were taken fundus pictures before sacrifice. Immunohistochemistry was performed to study the localization and expression of complement C3d. Morphology assessment of retina tissues were observed by standard microscope through hematoxylin-eosin (H&E) staining
Results
geographic retinal atrophy, significant increase in thickness of bruch membrane, and deposits of complement C3d were observed in control mice and in mice injected with AAV-LacZ 3 months after immunization of CEP. Mice injected with HO-1had less retinal degeneration, preserved the structure of retinal pigment epithelium (RPE) and bruch membrane, and attenuated the deposits of complement C3d in bruch membrane.
Conclusions
HO-1 gene therapy conferred protection on RPE in a mice model of atrophic AMD through immunized by CEP.
Keywords: 538 gene transfer/gene therapy •
412 age-related macular degeneration •
438 Bruch's membrane