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Isaac Vidal Paredes, Carlos Daniel Diaz Palomera, Jose Navarro Partida, Arturo Santos, Juan Armendariz Borunda; Evaluation of pirfenidone and pirfenidone-loaded liposomes for treating chemical corneal injury. Invest. Ophthalmol. Vis. Sci. 2021;62(8):941.
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An aberrant fibrotic repair process after a chemical corneal burn may lead to corneal opacity, inflammation and neovascularization and, therefore, vision impairment. Pirfenidone is clinically approved antifibrotic and anti-inflammatory drug for the treatment of idiopathic pulmonary fibrosis. We evaluated the effect of pirfenidone on human corneal fibroblast (HCF) treated with TGFβ. We also tested the effect of pirfenidone and pirfenidone-loaded liposomes against alkali burn-induced corneal damage in mice.
HCF primary cultures were established from human donor corneas. HCFs were treated with TGFβ1 (5ng/ml) to induce myofibroblastic transformation and fibrosis for 7 days under serum-free conditions. Cultures were treated with pirfenidone at two concentrations (100 and 300 µM) α-SMA mRNA expression levels were measured using Real-time quantitative PCR.C57BL/6 mice were treated with 0.5 N NaOH to the cornea for 30 seconds. Pirfenidone (100 µM) and pirfenidone-loaded liposomes (100 µM) were administered topically to damaged corneas four times a day during 14 days. Corneal opacity and neovascularization were clinically evaluated at 24, 48 hours, and 2 weeks after chemical burn injury. Histology of corneas was performed after day 14 and corneal thickness, neovascularization, inflammatory infiltrate, edema and goblet cell differentiation of corneal epithelium was evaluated with hematoxylin and eosin and Masson stains.
Pirfenidone at 100 µM significantly reduced α-SMA mRNA levels (p < 0.5) in HCF cultures. Both pirfenidone and pirfenidone-loaded liposomes reduced corneal opacity and neovascularization, as well as histologic corneal thickness, neovascularization, inflammatory infiltrate, edema and goblet cell differentiation of corneal epithelium in mice models, however, liposome-free pirfenidone showed a more pronounced improvement.
Pirfenidone and pirfenidone-loaded liposomes have the potential to treat chemical corneal injury, however, further evaluations of liposome effectiveness are warranted.
This is a 2021 ARVO Annual Meeting abstract.
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