Retinal vascular alterations in HbSC and HbSS mice. (A) Representative whole mount fluorescence images of retinas from 12-month-old HbAA, HbSC, and HbSS mice. HbAA retina (left) showing normal vasculature with well-defined major vessels radiating from the central optic nerve head (orange arrows), uniform branching, and no significant dropout. HbSC and HbSS retinas (middle and right) show reduced numbers of major vessels with irregular thickness (green arrows), peripheral vascular dropout (orange circles), and central-retinal/midretinal vascular dropout (blue circles). Scale bars, 1 mm. (B) Pathological grading on retinal vascular alterations in 12-month-old HbAA, HbSC, and HbSS mice based on vessel morphology, density, and the presence of avascular regions. (C-D) Representative confocal image (C) and reconstructed image generated with an automated pipeline (D) for quantification of retinal vascular branching (scale bar, 100 μm). (E) Quantification of vascular branching in HbAA, HbSC, and HbSS mice (HbAA, n = 4; HbSC, n = 4; HbSS, n = 4). Comparisons to HbAA mice are indicated in black; comparisons between HbSC and HbSS mice are indicated in blue. ∗P < .05. ns, no significant difference.