Comparison of Albino and Pigmented Rat Oxygen-Induced Retinopathy Models: From Vascular to Neural Retinal Changes

Purpose: To compare two commonly used rat models of oxygen-induced retinopathy (OIR)-the 50/10 model in Sprague-Dawley rats and the 80/40 model in Long-Evans rats-to identify which more closely reproduces the features of human retinopathy. Methods: Dams and pups were exposed from postnatal day 0 (P0) to P14 to alternating oxygen cycles, followed by analyses at P14, P18, and P28. The 50/10 protocol alternated 50% and 10% oxygen every 24 hours, whereas the 80/40 protocol alternated 80% and 40% oxygen every 12 hours. The vascular, structural, and functional retinal changes were assessed using in vivo imaging and electrophysiology, as well as ex vivo histological and molecular analyses. Results: Both OIR protocols induced significant retinal vascular abnormalities compared with controls, but with marked differences in onset, severity, and persistence. The 50/10 protocol produced earlier and more sustained vascular alterations, including reduced vascular coverage, increased vascular tortuosity, and neovascularization beginning at P14. Similar vascular changes appeared later and were less persistent in the 80/40 model. Retinal thinning occurred in both models; however, long-term photoreceptor segment thinning was observed only in the 50/10 protocol. The 50/10 protocol was associated with increased retinal cell death, significant cone photoreceptor loss, and mostly reduced electroretinographic responses, findings that were not observed in the 80/40 protocol. Conclusions: Both OIR models replicate features of human pathology, but differ in disease dynamics. These differences should be considered when selecting an OIR protocol, depending on whether vascular pathology or neurodegeneration is the primary therapeutic target.