Strain-Dependent Differences in Baseline Retinal Immune Homeostasis: A Comparative Study of Albino and Pigmented Mice

Mouse models are essential for glaucoma research; however, strain-dependent biological differences may complicate the interpretation and translational value of experimental findings. Because baseline retinal immune tone can shape the response to ocular hypertension (OHT), defining constitutive inflammatory profiles across commonly used mouse strains is critical. Basal intraocular pressure (IOP), retinal interleukin (IL)-1β, interferon gamma (IFN-γ), IL-6, IL-4, IL-10, and vascular endothelial growth factor (VEGF) levels by Luminex xMAP, and the cellular localization of inflammatory mediators by immunofluorescence using Iba-1, GFAP, Brn3a, NF-200, and VEGFR1 were compared between male albino Swiss CD1 and pigmented C57BL/6J mice. Basal IOP did not differ between strains, whereas the basal retinal immune environment did. CD1 mice showed higher IL-1β and IL-4 levels and detectable IFN-γ, whereas C57BL/6J mice showed higher IL-6, IL-10, and VEGF levels. Immunofluorescence revealed strain-specific localization: in CD1 retinas, IL-1β was detected in microglia and macroglia, IFN-γ in microglia, and IL-6 mainly in microglia; in C57BL/6J retinas, IL-1β and IL-6 were mainly associated with macroglia (Müller cells and astrocytes), and IL-4 with microglia. In both strains, IL-10 localized to NF-200-positive axons and VEGFR1 to glial fibrillary acidic protein (GFAP)-positive macroglia. Despite similar basal IOP, albino Swiss CD1 and pigmented C57BL/6J mice differ markedly in their basal retinal immune profiles. Albino mice show a more reactive baseline state, whereas pigmented mice display tighter immunoregulation and stronger immune-vascular support. Strain selection is therefore critical for experimental design, data interpretation, and translational relevance to ensure preclinical findings translate into human outcomes.