Metabolic Syndrome Predisposes Ossabaw Minipig Retina to an Early Neurodegenerative Milieu

The miniature (mini) Ossabaw pigs are proposed as a translational preclinical model for testing and developing novel therapeutics for human diseases, including cystic fibrosis, cancer, and metabolic syndrome (MetS). In recent years, pigs have gained similar attention for studying retinal abnormalities and disorders owing to their close resemblance in size, anatomy, vasculature, and pathology to the human eye compared with their rodent counterparts. In our previous study, Ossabaw minipigs fed a Western diet for 10 weeks and followed for 3.5 months exhibited early signs of retinal degeneration and vascular abnormalities, mimicking the early stages of diabetic retinopathy (DR). To further evaluate pathomorphological alterations across neuronal and non-neuronal cell types, the present study comprehensively investigated individual retinal layers using cell-type-specific immunostaining. We found that the Western diet-fed mini pigs had reduced rhodopsin and blue opsins, changes in bipolar and ganglion cells, and reduced density of pre- and post-synaptic connections. Moreover, the retinas of obese mini pigs showed evidence of gliosis and microglial activation. Our findings suggest that a Western diet-induced metabolic disorder exhibits an early neurodegenerative milieu and further demonstrate the suitability of Ossabaw mini pigs as a model for human retinal diseases associated with MetS, such as DR and diabetic macular edema (DME).