Ossabaw minipig on a long-term Western diet unveil characteristics of diabetic retinopathy progression

Abstract

Purpose : Diabetic retinopathy (DR) is a multi-factorial neurodegenerative and microvascular retinal disorder that elicits an immune response linked to inflammation. Recent studies demonstrate that Ossabaw minipigs showed a propensity to develop type 2 diabetes and metabolic syndrome on exposure to the Western diet. Our previous study demonstrated increased plasma S100A9 levels in DR patients and neurodegenerative changes in the Ossabaw retina, suggesting early-onset DR in obese pigs compared to their lean counterparts. This study further establishes the Ossabaw minipig as a preclinical model of diabetic retinopathy progression for six months when fed on a Western diet.

Methods : Ossabaw mini pigs were exposed to a Western diet consisting of high- kilocalorie/high-fat/high-fructose corn syrup food up to 7500 kcal/day intake. Western diet includes an increase of 16.2% in protein, 40.8% in carbohydrates, and 43% in fat for six months compared to their lean counterpart. Lean mini pigs were fed with the standard 2400 kcal/day intake of 8.5% protein, 71.0% carbohydrate, and 10.5% fat. Blood samples and eye tissue were obtained after euthanization for blood profiling and cellular and biochemical assessment of DR pathology. ELISA assay measured S100A9 protein levels in the plasma. Retinal whole mount, trypsin digest, and immunohistochemistry (IHC) were performed to assess the retina’s acellular capillaries, microvascular, and structural integrity.

Results : Ossabaw minipigs fed on a Western diet displayed increased levels of S100A9 protein in the plasma compared to a lean diet after six months. Obese minipigs also showed degenerative changes in the retina. Retinal whole mount displayed loss in vessel percentages, total vessel length, and lacunarity.

Conclusions : Ossabaw minipigs fed on a Western diet displayed cellular and biochemical alterations attributing to DR progression in the retina.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.