Multimodal retinal imaging evaluation of macular degeneration persistent disease activity animal model in Watanabe heritable hyperlipidemic rabbits.

The Watanabe Heritable Hyperlipidemic (WHHL) rabbit, a model for familial hypercholesterolemia, offers a unique opportunity to study lipid metabolism disorders and their ocular effects. This study employed multimodal imaging, including color fundus photography, fluorescein angiography, indocyanine green angiography, photoacoustic microscopy (PAM), and optical coherence tomography (OCT), to longitudinally assess WHHL rabbit eyes over one year. Given its relevance to persistent disease activity (PDA) in age-related macular degeneration (AMD), WHHL rabbits were evaluated as a potential model for PDA-associated AMD. Choroidal neovascularization (CNV) was induced in WHHL rabbits via subretinal injection of VEGF and Matrigel, followed by bevacizumab (Bev) treatment. A progressive lipid layer developed in the cornea by month 7. Histological analysis revealed significant outer nuclear layer cell loss in WHHL rabbits compared to wild-type (WT) controls. OCT imaging demonstrated increased CNV thickness in WHHL rabbits, consistent with PDA. Bev treatment reduced CNV leakage by 90.13 % in WT rabbits but only 16 % in WHHL rabbits, indicating treatment resistance. PAM at 780 nm effectively distinguished CNV from surrounding microvasculature, while OCT provided detailed retinal imaging. Although rabbits lack a fovea, the WHHL model demonstrates key features of wet AMD, including PDA and reduced anti-VEGF response. Our findings support WHHL rabbits as a promising preclinical model for studying lipid-related retinal diseases, AMD pathophysiology, and treatment resistance, advancing research into novel therapeutic strategies.