Polyunsaturated Fatty Acid Balance Modulates Microglial State in a Murine Model of Oxygen-Induced Neovascularization

Area of Science:

• Ophthalmology
• Neuroscience
• Molecular Biology

Background:

• The retina requires polyunsaturated fatty acids (PUFAs) for vision.
• Dietary omega-3 and omega-6 PUFAs may protect against retinopathy of prematurity (ROP).

Purpose of the Study:

• To elucidate mechanisms by which altering omega-6 and omega-3 PUFAs in the eye protects against pathologic retinal neovascularization (NV).

Main Methods:

• Utilized transgenic fat-1 mice converting omega-6 to omega-3 PUFAs in an oxygen-induced retinopathy (OIR) model.
• Employed immunofluorescence, bulk retinal RNA sequencing, and lipid mediator profiling (UHPLC-MS/MS).

Main Results:

• Fat-1 OIR mice showed significantly reduced vaso-obliteration and neovascularization compared to WT OIR mice.
• Fat-1 mice exhibited a dampened transcriptional response to OIR, with attenuated pathways in angiogenesis, inflammation, and microglial activation.
• Differential expression of lipid mediators, including ARA-derived oxylipins and EPA-derived specialized pro-resolving mediators, was observed.

Conclusions:

• A lower omega-6:omega-3 ratio protects against retinal neovascularization.
• This protection is linked to reduced hyperoxia-induced microglial activation, inflammation, and angiogenic signaling.