High-Fat Diet-Induced Lipid Metabolic Dysregulation Activates Inflammatory Signaling Pathways Regulating Ocular Growth

Background Myopia has become a major global public health concern, with increasing evidence linking diet and inflammation to its development. Objective To investigate the effects of a high-fat diet (HFD) on refractive development and myopia progression in guinea pigs. Methods Thirty-two 3-week-old pigmented guinea pigs were randomly assigned to four groups: Control, HFD, lens-induced myopia (LIM), and lens-induced myopia with high-fat diet (LIM + HFD) group. The HFD group was fed a high fat diet for 4 weeks, while myopia was induced in the right eye of LIM and LIM + HFD groups using a -10D lens. Ocular parameters, including refractive error (RE), axial length (AL), retinal thickness (RT), choroidal thickness (ChT), and choroidal blood perfusion (ChBP), were measured at baseline, 2 and 4 weeks. Serum lipids (TC, TG, HDL, LDL) were assessed using an automated biochemical analyzer and serum and retinal levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and nuclear factor kappa-B (NF-kB) were evaluated by ELISA and qPCR at baseline and 4 weeks. Results After 4 weeks, HFD and LIM + HFD groups developed dyslipidemia with elevated TC, TG, and LDL (P < 0.01). Compared with controls, the HFD group showed decreased RE, increased AL, and reduced RT, ChT, and ChBP (P < 0.0001), indicating greater susceptibility to myopia. In lens-wearing eyes, LIM + HFD did not exacerbate myopic progression compared with LIM (P > 0.05). However, in fellow eyes, LIM + HFD induced HFD-like structural and functional changes, significantly different from LIM alone (P < 0.001). ELISA and qPCR revealed elevated IL-1β, IL-6, and NF-kB in HFD and LIM groups, with the highest levels in LIM + HFD. Conclusions A 4-week HFD increased susceptibility to myopia during normal refractive development but did not worsen lens-induced myopia. HFD was associated with enhanced systemic and retinal inflammation, suggesting a potential link between diet-induced inflammation and increased myopia susceptibility.