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A comprehensive review of the effects of tacrolimus (FK-506) on dry eye disease (DED): Focus on inflammation and biochemical processes
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  • Maryam Golmohammadi,
  • Mehraveh Sadeghi Ivraghi,
  • Saade Abdalkareem Jasim,
  • Yasser Fakri Mustafa,
  • Zahraa F. Hassan,
  • Munther Abosaooda,
  • Hamidreza Seif,
  • Ahmed Hamed Salman,
  • Pallavi Ghildiyal,
  • Mohammad Yasin Zamanian
Maryam Golmohammadi
Shahid Beheshti University of Medical Sciences School of Medicine
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Mehraveh Sadeghi Ivraghi
Qazvin University of Medical Sciences Qazvin Medical School
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Saade Abdalkareem Jasim
Al-Mamoun University College
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Yasser Fakri Mustafa
University of Mosul College of Rights
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Zahraa F. Hassan
University of Al-Qadisiyah College of Dentistry
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Munther Abosaooda
Islamic University
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Hamidreza Seif
Hamadan University of Medical Sciences
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Ahmed Hamed Salman
Al-Bayan University
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Pallavi Ghildiyal
Uttaranchal University Institute of Management
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Mohammad Yasin Zamanian
Hamadan University of Medical Sciences

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Abstract

Dry eye disease (DED) represents a prevalent visual ailment, defined by insufficient wetting and lubrication of the ocular surface. The principal management strategy for dry eye involves the application of artificial tear solutions to mitigate eye discomfort. Moreover, immune-modulating agents such as cyclosporine A and tacrolimus (FK506) are employed in the therapeutic regimen for this condition. These drugs regulate the immune response and reduce ocular inflammation. Tacrolimus (TAC) is 10-100 times more effective than cyclosporine and has a better safety profile. Nevertheless, the modest aqueous solubility and substantial molecular size of TAC present obstacles to its efficient administration to the eye. Consequently, a range of TAC formulations including ointments, micelles, liposomes, and nanocarriers are under exploration to enhance ocular delivery. Findings from this investigation indicated that TAC impedes the secretion of pro-inflammatory cytokines and dampens immune activity by restraining the activation of T and B lymphocytes. Furthermore, TAC elevates goblet cell populations in the conjunctiva, pivotal for mucin production and the preservation of ocular surface integrity. Additionally, using TAC-loaded liposomes can further enhance its therapeutic efficacy by improving ocular bioavailability. Furthermore, 0.03% TAC eye drops applied directly to the eye successfully improve tear film stability and the health of the eye’s surface in patients with DED. Overall, TAC has shown promising effects in treating DED by reducing inflammation and improving tear secretion in experimental and clinical studies. However, more studies are needed to fully understand the mechanism of action and long-term effects of TAC on DED.