The Protective Effect of Topical Spermidine on Dry Eye Disease with Retinal Damage Induced by Diesel Particulate Matter2.5

Abstract

Air pollutants, especially ambient fine particulate matter2.5, may contribute to various ocular surface disorders, including dry eye disease, keratitis and conjunctivitis. A natural polyamine spermidine has a protective effect on the retina and optic nerve; however, no study has been conducted on the application of spermidine in particulate matter2.5-induced dry eye disease. In the present study, we investigated the effect of spermidine eye drops in topically exposed particulate matter2.5-induced dry eye models of Sprague-Dawley rats, by hematological, biochemical and histological evaluation. Spermidine eye drops attenuated the particulate matter2.5 exposure-induced reduction of tear secretion and corneal epithelial damage. Furthermore, spermidine protected against conjunctival goblet cell loss and retinal ganglion cell loss induced by particulate matter2.5. Additionally, spermidine markedly prevented particulate matter2.5-induced infiltration of cluster of differentiation3+ and cluster of differentiation4+ T lymphocytes and F4/80+ macrophages on lacrimal gland. Moreover, over expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6 and interleukin-17 in the lacrimal gland and cornea. Meanwhile, the levels of serum total cholesterol and low-density lipoprotein cholesterol were markedly increased by topical exposure to particulate matter2.5, but this change in the lipid profile was decreased by spermidine. Taken together, spermidine may have protective effects against particulate matter2.5-induced dry eye symptoms via stabilization of the tear film and suppression of inflammation and may in part contribute to improving retinal function and lipid metabolism disorder.

MSC-Derived Small Extracellular Vesicles Attenuate Autoimmune Dacryoadenitis by Promoting M2 Macrophage Polarization and Inducing Tregs via miR-100-5p

“…Macrophages are important regulators in inflammation of LGs ( 5 , 28 ). To clarify its underlying mechanism of how hUC-MSC-sEVs prevented the rabbit autoimmune dacryoadenitis, we investigated the effects of hUC-MSC-sEVs on macrophages accumulated in inflamed LGs.…”

Research Progress and Potential Applications of Spermidine in Ocular Diseases

“…In addition, spermidine has been proven to be a precursor for the essential enzymatic modification of eIF5A [ 54 ]. It may also play a positive role in stem cell function, such as the proliferation and migration of epithelial cells or slow-proliferating primary cultures [ 13 , 17 , 39 , 55 ], by stimulating. them to differentiate and prevent their senescence [ 23 ], partly through promoting entry into the S/G2-M phases of the cell cycle [ 14 , 38 ].…”

“…Recently, Lee et al applied spermidine (0.2, 0.5%) in the form of topical eye drops in a rat model of dry eye syndrome induced by fine particulate matter (aerodynamic diameter below 2.5 µm, PM 2.5 ) to simulate air pollution. The results showed that spermidine stabilized the tear film and suppressed ocular surface inflammation [ 17 ]. In that study, proinflammatory cytokines such as IL-6, TNF-α, and IL-17 in the lacrimal gland and corneal tissue were significantly reduced after topical administration of spermidine (20 µL of 0.2% or 0.5% spermidine, four times daily).…”

“…In that study, proinflammatory cytokines such as IL-6, TNF-α, and IL-17 in the lacrimal gland and corneal tissue were significantly reduced after topical administration of spermidine (20 µL of 0.2% or 0.5% spermidine, four times daily). In addition, cornea epithelial cells were prevented from falling off after spermidine administration [ 17 ].…”

“…In the light of such protective effects, researchers have recently expanded its application to ocular diseases such as dry eye syndrome, bacterial keratitis, cataracts, glaucoma, optic nerve injury, and age-related macular degeneration (AMD) [ 14 , 16 , 17 , 18 , 19 , 20 ]. These diseases pose a significant threat to human vision worldwide, especially among working-aged groups, thus exerting a heavy burden on families and society [ 21 , 22 ].…”