Authors:Ke Lan, Yang Yanning
Corresponding author: Yang Yanning, Email:ophyyn@163.com
Published:2026-10-10
DOI:10.3760/cma.j.cn115989-20250601-00178
ABSTRACT
Dry eye is a common, multifactorial, chronic ocular surface disease with diverse clinical manifestations, complex pathogenesis, and prolonged treatment cycles, which significantly impacts patients’ quality of life and visual quality. Therefore, the exploration of more effective treatments is of great urgency. Amino acids, as functional regulators of multiple metabolic processes, are endowed with antioxidant, anti-inflammatory, and repair-promoting properties, playing a crucial role in maintaining ocular surface homeostasis. Studies have demonstrated that the development and progression of dry eye primarily involves inflammation, and the regulatory functions of amino acids are closely linked to this process. A deeper understanding of the role of amino acids in the ocular surface and the pathogenesis of dry eye is of great clinical significance for developing more comprehensive dry eye treatment strategies. This article systematically describes the role of amino acids in ocular surface tissues, including the tear film, cornea, conjunctiva, meibomian glands, and lacrimal glands. We summarize the potential mechanisms of dry eye caused by abnormal amino acid metabolism, including imbalanced ocular antioxidant defenses, dysregulated inflammatory responses, impaired energy metabolism, and abnormal cell or tissue repair. We also provide an outlook on the potential application of amino acids in dry eye treatment, aiming to deepen ophthalmologists’ understanding of the interaction between amino acids and dry eye and provide a theoretical basis for enriching clinical treatment options for dry eye.
KEYWORDS：
Amino acids;Dry eye;Ocular surface;Pathogenesis;Treatment
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Authors Info & Affiliations
Ke Lan
Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan 430060, China
Ke Lan now works at Wuhan Aier Hankou Eye Hospital, Wuhan 430000, China
Yang Yanning
Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan 430060, China
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References
[1] Yang W, Wang H, Li J, et al. Demographic and lifestyle factors associated with dry eye disease in China: a cross‐sectional multi-center study[J]. Ocul Surf, 2024, 34∶ 146-155. DOI: 10.1016/j. jtos. 2024.07.007.
▼click to see more references
[2] Kim CE, Kleinman HK, Sosne G, et al. RGN-259 (thymosin β4) improves clinically important dry eye efficacies in comparison with prescription drugs in a dry eye model[J]. Sci Rep, 2018, 8(1):10500. DOI: 10.1038/s41598-018-28861-5.
[3] Chen X, Zhang C, Peng F, et al. Identification of glutamine as a potential therapeutic target in dry eye disease[J]. Signal Transduct Target Ther, 2025, 10(1):27. DOI: 10.1038/s41392-024-02119-1.
[4] Song X, Liang Y, Zhou S, et al. Glutamine alleviates lipopolysaccharide-induced corneal epithelial inflammation and oxidative stress in dogs[J]. Exp Eye Res, 2023, 234:109607. DOI: 10.1016/j.exer.2023.109607.
[5] Aragona P, Rania L, Roszkowska AM, et al. Effects of amino acid-enriched tear substitutes on the cornea of patients with dysfunctional tear syndrome[J]. Acta Ophthalmol, 2013, 91(6):e437-444. DOI: 10.1111/aos.12134.
[6] Nakatsukasa M, Sotozono C, Shimbo K, et al. Amino acid profiles in human tear fluids analyzed by high-performance liquid chromatography and electrospray ionization tandem mass spectrometry[J]. Am J Ophthalmol, 2011, 151(5):799-808. DOI: 10.1016/j.ajo.2010.11.003.
[7] Ling ZN, Jiang YF, Ru JN, et al. Amino acid metabolism in health and disease[J]. Signal Transduct Target Ther, 2023, 8(1):345. DOI: 10.1038/s41392-023-01569-3.
[8] Hodges RR, Dartt DA. Tear film mucins: front line defenders of the ocular surface; comparison with airway and gastrointestinal tract mucins[J]. Exp Eye Res, 2013, 117:62-78. DOI: 10.1016/j.exer.2013.07.027.
[9] ChenZhuo L, Murube J, Latorre A, et al. Different concentrations of amino acids in tears of normal and human dry eyes[J]. Adv Exp Med Biol, 2002, 506(Pt A):617-621. DOI: 10.1007/978-1-4615-0717-8_87.
[10] Achour S, Hosni Z, Darghouthi S, et al. Assisted dipeptide bond formation: glycine as a case study[J]. Heliyon, 2021, 7(6):e07276. DOI: 10.1016/j.heliyon.2021.e07276.
[11] Zysset-Burri DC, Schlegel I, Lincke JB, et al. Understanding the interactions between the ocular surface microbiome and the tear proteome[J]. Invest Ophthalmol Vis Sci, 2021, 62(10):8. DOI: 10.1167/iovs.62.10.8.
[12] Gukasyan HJ, Kim KJ, Lee VH, et al. Glutathione and its transporters in ocular surface defense[J]. Ocul Surf, 2007, 5(4):269-279. DOI: 10.1016/s1542-0124(12)70093-9.
[13] Rusciano D, Roszkowska AM, Gagliano C, et al. Free amino acids: an innovative treatment for ocular surface disease[J]. Eur J Pharmacol, 2016, 787:9-19. DOI: 10.1016/j.ejphar.2016.04.029.
[14] Wu G, Bazer FW, Burghardt RC, et al. Proline and hydroxyproline metabolism: implications for animal and human nutrition[J]. Amino Acids, 2011, 40(4):1053-1063. DOI: 10.1007/s00726-010-0715-z.
[15] Ottani V, Martini D, Franchi M, et al. Hierarchical structures in fibrillar collagens[J]. Micron, 2002, 33(7-8):587-596. DOI: 10.1016/s0968-4328(02)00033-1.
[16] Avila A, Nguyen L, Rigo JM. Glycine receptors and brain development[J]. Front Cell Neurosci, 2013, 7:184. DOI: 10.3389/fncel.2013.00184.
[17] Dudakova L, Liskova P, Trojek T, et al. Changes in lysyl oxidase (LOX) distribution and its decreased activity in keratoconus corneas[J]. Exp Eye Res, 2012, 104:74-81. DOI: 10.1016/j.exer.2012.09.005.
[18] Hulgan S, Jalan AA, Li IC, et al. Covalent capture of collagen triple helices lysine-aspartate and lysine-glutamate pairs[J]. Biomacromolecules, 2020, 21(9):3772-3781. DOI: 10.1021/acs.biomac.0c00878.
[19] Mohan RR, Gupta R, Mehan MK, et al. Decorin transfection suppresses profibrogenic genes and myofibroblast formation in human corneal fibroblasts[J]. Exp Eye Res, 2010, 91(2):238-245. DOI: 10.1016/j.exer.2010.05.013.
[20] 韩涵, 何宇茜, 张妍. 小分子亮氨酸重复蛋白聚糖家族在维持角膜透明性中的作用[J]. 中华实验眼科杂志, 2022, 40(3):266-270. DOI: 10.3760/cma.j.cn115989-20210222-00124. Han H, He YX, Zhang Y. Effects of small leucine-rich proteoglycans on corneal transparency[J]. Chin J Exp Ophthalmol, 2022, 40(3):266-270. DOI: 10.3760/cma.j.cn115989-20210222-00124.
[21] Meduri A, Aragona P, Grenga PL, et al. Effect of basic fibroblast growth factor on corneal epithelial healing after photorefractive keratectomy[J]. J Refract Surg, 2012, 28(3):220-223. DOI: 10.3928/1081597X-20120103-02.
[22] Katragadda S, Talluri RS, Pal D, et al. Identification and characterization of a Na+-dependent neutral amino acid transporter, ASCT1, in rabbit corneal epithelial cell culture and rabbit cornea[J]. Curr Eye Res, 2005, 30(11):989-1002. DOI: 10.1080/02713680500306439.
[23] Tedesco L, Rossi F, Ruocco C, et al. An original amino acid formula favours in vitro corneal epithelial wound healing by promoting Fn1, ITGB1, and PGC-1α expression[J]. Exp Eye Res, 2022, 219:109060. DOI: 10.1016/j.exer.2022.109060.
[24] Parra F, Kormanovski A, Guevara-Balcazar G, et al. Protective role of glutathione and nitric oxide production in the pathogenesis of pterygium[J]. J Ophthalmol, 2020, 2020:9638763. DOI: 10.1155/2020/9638763.
[25] Gukasyan HJ, Kannan R, Lee VH, et al. Regulation of L-cystine transport and intracellular GSH level by a nitric oxide donor in primary cultured rabbit conjunctival epithelial cell layers[J]. Invest Ophthalmol Vis Sci, 2003, 44(3):1202-1210. DOI: 10.1167/iovs.02-0409.
[26] Nucci C, Palamara AT, Ciriolo MR, et al. Imbalance in corneal redox state during herpes simplex virus 1-induced keratitis in rabbits. Effectiveness of exogenous glutathione supply[J]. Exp Eye Res, 2000, 70(2):215-220. DOI: 10.1006/exer.1999.0782.
[27] Liu S, Richards SM, Lo K, et al. Changes in gene expression in human meibomian gland dysfunction[J]. Invest Ophthalmol Vis Sci, 2011, 52(5):2727-2740. DOI: 10.1167/iovs.10-6482.
[28] Benítez Del Castillo JM, Pinazo-Duran MD, Sanz-González SM, et al. Tear 1H nuclear magnetic resonance-based metabolomics application to the molecular diagnosis of aqueous tear deficiency and meibomian gland dysfunction[J]. Ophthalmic Res, 2021, 64(2):297-309. DOI: 10.1159/000510211.
[29] Ohno Y, Satoh K, Shitara A, et al. Arginase 1 is involved in lacrimal hyposecretion in male NOD mice, a model of Sjögren’s syndrome, regardless of dacryoadenitis status[J]. J Physiol, 2020, 598(21):4907-4925. DOI: 10.1113/JP280090.
[30] Akyol-Salman I, Azizi S, Mumcu U, et al. Efficacy of topical N-acetylcysteine in the treatment of meibomian gland dysfunction[J]. J Ocul Pharmacol Ther, 2010, 26(4):329-333. DOI: 10.1089/jop.2010.0001.
[31] Akyol-Salman I, Azizi S, Mumcu UY, et al. Comparison of the efficacy of topical N-acetyl-cysteine and a topical steroid-antibiotic combination therapy in the treatment of meibomian gland dysfunction[J]. J Ocul Pharmacol Ther, 2012, 28(1):49-52. DOI: 10.1089/jop.2010.0110.
[32] Liu S, Tang S, Yang G, et al. Lysine demethylase 1B promotes tear secretion disorder in Sjogren’s syndrome by regulating the PAX6/CLU axis[J]. J Mol Neurosci, 2023, 73(1):28-38. DOI: 10.1007/s12031-022-02094-8.
[33] Ogawa K, Ohno Y, Tagashira A, et al. Blueberry stem extract prevents lacrimal hyposecretion in non-obese diabetic mice via activation of AMPK[J]. In Vivo, 2023, 37(3):1003-1015. DOI: 10.21873/invivo.13174.
[34] Dammak A, Pastrana C, Martin-Gil A, et al. Oxidative stress in the anterior ocular diseases: diagnostic and treatment[J]. Biomedicines, 2023, 11(2):292. DOI: 10.3390/biomedicines11020292.
[35] Chen X, Zhang C, Tian L, et al. In situ metabolic profile and spatial distribution of ocular tissues: new insights into dry eye disease[J]. Ocul Surf, 2022, 24:51-63. DOI: 10.1016/j.jtos.2021.12.013.
[36] Feng L, Li W, Liu Y, et al. Protective role of phenylalanine on the ROS-induced oxidative damage, apoptosis and tight junction damage via Nrf2, TOR and NF-κB signalling molecules in the gill of fish[J]. Fish Shellfish Immunol, 2017, 60:185-196. DOI: 10.1016/j.fsi.2016.11.048.
[37] Marchitti SA, Chen Y, Thompson DC, et al. Ultraviolet radiation: cellular antioxidant response and the role of ocular aldehyde dehydrogenase enzymes[J]. Eye Contact Lens, 2011, 37(4):206-213. DOI: 10.1097/ICL.0b013e3182212642.
[38] Tandon R, Vashist P, Gupta N, et al. Association of dry eye disease and sun exposure in geographically diverse adult (≥40 years) populations of India: the SEED (sun exposure, environment and dry eye disease) study-second report of the ICMR-EYE SEE study group[J]. Ocul Surf, 2020, 18(4):718-730. DOI: 10.1016/j.jtos.2020.07.016.
[39] Chen X, Rao J, Zheng Z, et al. Integrated tear proteome and metabolome reveal panels of inflammatory-related molecules via key regulatory pathways in dry eye syndrome[J]. J Proteome Res, 2019, 18(5):2321-2330. DOI: 10.1021/acs.jproteome.9b00149.
[40] Kim JC, Cheong TB, Park GS, et al. The role of nitric oxide in ocular surface diseases[J]. Adv Exp Med Biol, 2002, 506(Pt A):687-695. DOI: 10.1007/978-1-4615-0717-8_96.
[41] Jäger K, Garreis F, Posa A, et al. Functional relationship between cationic amino acid transporters and beta-defensins: implications for dry skin diseases and the dry eye[J]. Ann Anat, 2010, 192(2):65-69. DOI: 10.1016/j.aanat.2010.01.006.
[42] Gao X, Lee K, Reid MA, et al. Serine availability influences mitochondrial dynamics and function through lipid metabolism[J]. Cell Rep, 2018, 22(13):3507-3520. DOI: 10.1016/j.celrep.2018.03.017.
[43] Jiang Y, Yang C, Zheng Y, et al. A set of global metabolomic biomarker candidates to predict the risk of dry eye disease[J]. Front Cell Dev Biol, 2020, 8:344. DOI: 10.3389/fcell.2020.00344.
[44] Sosne G, Qiu P, Christopherson PL, et al. Thymosin beta 4 suppression of corneal NFκB: a potential anti-inflammatory pathway[J]. Exp Eye Res, 2007, 84(4):663-669. DOI: 10.1016/j.exer.2006.12.004.
[45] Sosne G, Ousler GW. Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, phase II clinical trial conducted using the controlled adverse environment (CAETM) model[J]. Clin Ophthalmol, 2015, 9:877-884. DOI: 10.2147/OPTH.S80954.
[46] Jin R, Li Y, Li L, et al. Anti-inflammatory effects of glycine thymosin β 4 eye drops in experimental dry eye[J]. Biomed Rep, 2020, 12(6):319-325. DOI: 10.3892/br.2020.1296.
[47] Kawakita T, Uchino M, Fukagawa K, et al. Randomized, multicenter, double-blind study of the safety and efficacy of 1% D-3-hydroxybutyrate eye drops for dry eye disease[J]. Sci Rep, 2016, 6:20855. DOI: 10.1038/srep20855.
[48] Bucolo C, Fidilio A, Platania C, et al. Antioxidant and osmoprotecting activity of taurine in dry eye models[J]. J Ocul Pharmacol Ther, 2018, 34(1-2):188-194. DOI: 10.1089/jop.2017.0008.
[49] Meduri A, Grenga PL, Scorolli L, et al. Role of cysteine in corneal wound healing after photorefractive keratectomy[J]. Ophthalmic Res, 2009, 41(2):76-82. DOI: 10.1159/000187623.
[50] Zhu R, Chen W, Gu D, et al. Chondroitin sulfate and L-cysteine conjugate modified cationic nanostructured lipid carriers: pre-corneal retention, permeability, and related studies for dry eye treatment[J]. Int J Biol Macromol, 2023, 228:624-637. DOI: 10.1016/j.ijbiomac.2022.12.238.
[51] Gu D, Zhou L, Zhang Y, et al. N-acetylcysteine and chitosan conjugate modified dexamethasone nanostructured lipid carriers: enhanced permeability, precorneal retention and lower inflammation for the treatment of dry eye syndrome[J]. Int J Biol Macromol, 2025, 299:140123. DOI: 10.1016/j.ijbiomac.2025.140123.