Branched-Chain Amino Acids Metabolism and Their Roles in Retinopathy: From Relevance to Mechanism

Abstract

Retinopathy is one of the leading causes of irreversible blindness and vision loss worldwide. Imbalanced nutrients play important roles in the pathogenesis and pathophysiology of retinal diseases. Branched-Chain Amino Acids (BCAAs), as essential amino acids, perform a variety of biological functions, including protein synthesis, glucose metabolism, lipid metabolism, inflammation, and oxidative stress in metabolic tissues of diabetes and aging-related diseases. Recently, it has been shown that BCAAs are highly related to neuroprotection, oxidative stress, inflammatory and glutamate toxicity in the retina of retinopathy. Therefore, this review summarizes the alterations of BCAA levels in retinopathy, especially diabetic retinopathy and aging-related macular disease, and the genetics, functions, and mechanisms of BCAAs in the retina as well as other metabolic tissues for reference. All of these efforts aim to provide fundamental knowledge of BCAAs for further discoveries and research on retina health based on the sensing and signaling of essential amino acids.

Causal relationships between blood metabolites and diabetic retinopathy: a two-sample Mendelian randomization study

“…We found causal relationships between seven metabolites in the amino acid metabolic pathway and DR. Amino acids participate in energy metabolism and regulate various metabolic pathways through gluconeogenesis ( 30 ). Previous studies have highlighted the significant role of amino acids in DR ( 30 – 32 ). Our findings specifically focused on the roles of tryptophan (TRP) and kynurenines (KYN) in DR. TRP serves as a primary origin for a range of bioactive molecules, including KYN, 5-hydroxytryptamine, melatonin, niacin and indoles ( 33 ).…”

Redox Regulation of Immunometabolism in Microglia Underpinning Diabetic Retinopathy

“…The activation of microglia is stimulated by extracellular signals, among which glucose and its derivative metabolites figure prominently [45][46][47][48]. Chronic hyperglycemia activates complex pathophysiologic processes in DR, comprising ischemia, hypoxia, dyslipidemia, and advanced glycation end products (AGEs).…”

“…In recent years, the emerging literature on immunometabolism is defining new roles for cellular metabolic pathways in microglia polarization in DR [25,45,46,48,63]. Immunometabolism indicates the metabolic processes within immune cells, thereby influencing the destiny and functional outcomes of these cellular entities [64][65][66].…”

Unveiling the gut-eye axis: how microbial metabolites influence ocular health and disease

“…Catabolism of BCAAs provides nitrogen for the synthesis of glutamate, and glutamate plays an important role in DR neurodegeneration as it is the major excitatory neurotransmitter in the CNS and retina. Branched chain amino acids (BCAAs) are associated with glutamate toxicity contributing to retinopathy (160), especially in DR and AMD. It has been found that BCAA supplements play a neuroprotective role by enhancing retinal ganglion cell survival, in addition to inflammatory and oxidative stress protective effects (160).…”

“…Branched chain amino acids (BCAAs) are associated with glutamate toxicity contributing to retinopathy (160), especially in DR and AMD. It has been found that BCAA supplements play a neuroprotective role by enhancing retinal ganglion cell survival, in addition to inflammatory and oxidative stress protective effects (160). BCAAs from protein diets are absorbed by the intestine, thus any dysregulation in absorption through altered gut microbiomes or intestinal malabsorption syndromes could be implicated in lower BCAA levels and susceptibility to retinopathy.…”