Malondialdehyde-Modified Photoreceptor Outer Segments Promote Choroidal Neovascularization in Mice.

PURPOSE

This study aimed to establish a novel choroidal neovascularization (CNV) mouse model through subretinally injecting malondialdehyde (MDA)-modified photoreceptor outer segments (POS), which was more consistent with the pathogenesis of wet age-related macular degeneration (AMD).

METHODS

MDA-modified POS were subretinally injected in C57BL/6J mice. Four weeks later, to assess the volume of CNV and the morphology of retinal pigment epithelium (RPE), isolectin B4 and zonula occludens-1 antibody were used for immunostaining. Fundus fluorescent angiography and optical coherence tomography imaging were used to describe the morphologic features of CNV. Transepithelial resistance was measured on polarized ARPE-19 cells. Vascular endothelial growth factor levels in the cell culture medium were detected by enzyme-linked immunosorbent assay. The protein and messenger RNA expression levels of autophagy markers were measured using Western blot and quantitative polymerase chain reaction.

RESULTS

CNV and RPE atrophy were successfully induced in the mouse model. MDA-modified POS also significantly increased the expression of vascular endothelial growth factor and disrupted cell junctions in RPE cells. In addition, MDA-modified POS induced autophagy-lysosomal impairment in RPE cells.

CONCLUSIONS

Subretinal injection of MDA-modified POS may generate a feasible CNV model that simulates the AMD pathological process.

TRANSLATIONAL RELEVANCE

This study expands the understanding of the role of MDA in AMD pathogenesis, which provides a potential therapeutic target of AMD.