A Preliminary Study On The Regulation Of Retinal And Choroidal Neovascularization By Amino Acid Metabolism

Objective: Retinal and choroidal neovascular diseases,such as diabetic retinopathy(DR),retinopathy of prematurity(ROP),and agerelated macular degeneration(AMD),are one of the main causes of visual impairment and even blindness.This study intends to preliminarily explore the role and mechanism of amino acids in retinal and choroidal neovascularization.Methods: We detected the levels of amino acids and their derivatives in retinal tissues at different time points in a mouse model of oxygeninduced retinopathy(OIR)by targeted metabolomics.Using human retinal pigment epithelium cell lines ARPE-19 and Müller glial cell lines MIOM1 as well as laser-induced choroidal neovascularization(CNV)and OIR mouse models,by limiting and supplementing amino acids,combined with experimental techniques such as RT-q PCR,WB,and immunofluorescence staining,the expression levels of angiogenesis molecules such as VEGF and related pathway signaling proteins were detected,and the role of amino acid and branched-chain amino acid metabolism on retinal and choroidal neovascularization was preliminarily explored.Results: Targeted metabolomics showed that the levels of amino acids and their derivatives in retinal tissue of OIR mice did not change significantly at postnatal day(P)12 compared with the control group,while on P13,P17,and P42,the levels of amino acids and their derivatives were significantly changed.In in vitro studies,amino acids(AA)deprivation and branched-chain amino acids(BCAA)deprivation up-regulated VEGF m RNA expression levels in ARPE-19 and MIO-M1 cells,and were associated with up-regulation of phosphorylated AKT and ATF4.In OIR and CNV mouse models,feeding low AA and low BCAA diets promoted retinal and choroidal neovascularization compared with controls,whereas supplementation with a BCAA mixture inhibited choroidal neovascularization.Conclusion: This study preliminarily shows that the metabolism of AA and BCAA is involved in the formation of retinal and choroidal neovascularization.The dietary intervention of AA and BCAA has an important regulatory effect on retinal and choroidal neovascularization,which provides new ideas for the therapy of neovascular diseases.