# The Protective Effect of Polyunsaturated Fatty Acids against Dry Eye Disease: A Literature Review
###### Abstract  
Dry eye disease (DED) is a common disease, and have an adverse effect the physical, functional, and psychological quality of life. It is a multifactorial disorder characterized by the loss of tear film homeostasis, in which self-perpetuating vicious cycle leads to deterioration of function and inflammation of the lacrimal functional unit. Hence, treatment strategies should be aimed at the interruption of the vicious inflammatory cycle and alleviation of ocular surface inflammation. Anti-inflammatory therapies have been shown to improve the signs and symptoms of the disease. Evidence indicates that polyunsaturated fatty acids (PUFAs) may contribute to reinforcement of innate anti-inflammatory mechanisms, and systemic and topical administration of PUFAs may help modulate ocular surface inflammation. In the present review, the authors will introduce the results of clinical and experimental studies to elucidate the mechanism, efficacy, and safety of systemic and topical supplementation with PUFAs as an alternative therapeutic strategy for DED. This review will also include discussion regarding current perspectives, including evidence-based recommendations and possible side effects of PUFAs supplementation. The review of the literature suggests that PUFAs supplementation can be a viable option for the treatment of DED, although further studies are needed for establishment of treatment guidelines.  
dry eye; dry eye disease; essential fatty acids; ocular surface; omega-3; polyunsaturated fatty acids +
Footnote †: journal:  
homeostasis caused by ocular surface desiccation triggers the activation of an inflammatory cascade involving the ocular surface epithelium and residing immune cells: promotion of the production of innate inflammatory mediators, such as matrix metalloproteinases (MMPs), cytokines (e.g., tumor necrosis factor (TNF-\(\alpha\)) and interleukin (IL)-1\(\beta\)) and chemokines (e.g., C-X-C motif ligand (CXCL) 9 (monokine induced by gamma interferon [MIG]), CXCL10 (Interferon gamma-induced protein [IP]-10) and C-C motif ligand (CCL) 20 (Macrophage Inflammatory Protein [MIP] 3\(\alpha\))); activation of inflammatory cells (e.g., CD4+ T cells); maturation of dendritic cells, which may initiate a vicious self-perpetuating inflammatory cycle that eventually leads to further deterioration of ocular surface inflammation and damage [6; 12; 13; 14].  
Hence, the treatment approaches focused on breaking the vicious inflammatory cycle can conceivably be effective for DED [6]. Artificial tears can relieve ocular surface inflammation by reducing tear osmolarity and diluting inflammatory mediators on the ocular surface, although they may not be the definitive treatment for the self-perpetuating inflammation on the ocular surface [6]. Systemic and topical and systemic administration of anti-inflammatory drugs, such as cyclosporine A, corticosteroids, and lifitegrast have been applied for the alleviation of the ocular surface symptoms and signs [6].  
Therapeutic approaches aimed at reinforcing the endogenous anti-inflammatory and immunomodulatory mechanisms may also be helpful [14]. Previous studies have shown that oral and topical administration of omega-3 (\(\omega\)3) and omega-6 (\(\omega\)6) polyunsaturated fatty acids (PUFAs) can decrease the concentrations of inflammatory mediators associated with DED, improve dry eye symptoms, restore tear film homeostasis, and facilitate corneal nerve regeneration, suggesting that supplementation with these PUFAs can be alternative treatment for DED [15; 16; 17; 18; 19; 20; 21; 22; 23; 24; 25; 26].  
In this literature review, we aim to introduce the studies regarding the influences of \(\omega\)3 and \(\omega\)6 PUFAs on DED and discuss the potential underlying mechanisms of PUFAs in the treatment of the disease.