Early life pre-disposition to diet-induced retinal pathology

Purpose: wildtype C57BL/6 mice fed an unhealthy high fat diet (HFD) for 12 months recapitulate salient age-related macular degeneration (AMD)-like features. As a HFD also causes obesity-linked illnesses in younger individuals, we sought to assess its effects in the retina at an earlier stage of the lifecourse.<br/><br/>Methods: 80 female mice were randomly allocated into two equal sized groups and fed either a standard rodent chow or a 45% kcal fat diet after weaning. Retinae were scrutinised at 8, 16 and 24 weeks old by optical coherence tomography (OCT) and fundoscopy. Retinal layers in OCT scans were quantified by automatic segmentation. Scotopic central field focal electroretinography (ERG) was performed at 24 weeks.<br/><br/>Results: OCT analysis at 8 weeks showed significantly thicker retinal neurofibrillary layer (RNFL: p=0.0467) and inner segment (IS) layers (p= 0.0085) in HFD mice, which were abolished at subsequent 16 and 24 week timepoints (n=10/group at each timepoint). 24 week ERG data showed reduced A (p= 0.0213) and B wave (p=0.0041) as well as delayed T(A) (p=0.0013) and T(B) (p=0.0109) implicit times (n=5 standard chow, n=11 HFD). No marked changes were observed in the fundus (n=10 for each cohort at each timepoint). Unpaired students t-test with Welch’s correction.<br/><br/>Conclusions: longitudinal analyses revealed early HFD-induced structural changes in the retina which were abolished with age. However, functional retinal deficits at 24 weeks, even in the absence of any structural abnormalities, showed that earlier pathology may predispose individuals to developing retinopathies such as AMD in later life. Our findings provide unexpected new insights, showing diet-induced priming effects that can contribute to complex retinopathies.<br/><br/>This abstract was presented at the 2025 ARVO Annual Meeting, held in Salt Lake City, Utah, May 4-8, 2025.