Diabetic retinopathy features in lund MetS rats

Abstract

Diabetic retinopathy; Metabolic syndrome; Neurodegeneration

Retinopatía diabética; Síndrome metabólico; Neurodegeneración

Retinopatia diabètica; Síndrome metabòlica; Neurodegeneració

The Lund MetS rat (BBDR.cg-Leprdb/db.cp/LundRj) is a novel animal model that has a congenic leptin receptor deficiency (LepR−/−) and males exhibit a variety of metabolic abnormalities mimicking the human metabolic syndrome, including hyperglycemia, dyslipidemia, severe obesity, and a type 2 diabetes-like condition from 14 weeks of age. However, whether Lund MetS rats (LM rats) develop diabetic retinopathy is still unknown. The purpose is to investigate the features of diabetic retinopathy in this model. In this study, male LM rats aged 15 and 30 weeks were analyzed for pathological retinal changes, including vasculopathy, inflammation, reactive gliosis, oxidative stress, and neurodegeneration features on the retinas by histological, immunohistochemical, and gene and protein expression analysis. Compared with the non-diabetic LM rats, diabetic LM rats, mainly at 30 weeks of age, had a decrease in retinal thickness and loss of retinal ganglion cells and photoreceptors, indicating retinal neurodegeneration. They also presented an increase in VEGF-A expression, Endra, Icam-1, Vcam-1, and Endrb vascular genes, and albumin suggesting neurovascular unit dysfunction. Furthermore, retinas presented reactive gliosis and infiltration of microglia, TNF-α-positive vessels and expressed elevated levels of inflammatory genes Tnf-α, IL-18 and IL-6, and oxidative stress markers Sod2 and 8-hydroxy-2-deoxyguanosine (8-OHdG). Our results suggest that diabetic LM rats reproduce the early neurodegenerative and altered neuro-vascular features that also occur in the human diabetic eye.

This research project was funded by grants from Instituto de Salud Carlos III (PI20/01588 and PI22/01747), Agència Gestió Ajuts Universitaris i de Recerca (2017SGR1303), and Ministerio de Ciencia e Innovación, Gobierno de España (PID2022-138544OB-100 and PID2021-122807OB-C32).