Dose-dependent therapeutic effects of topical 1,25 OH-vitamin D3 on corneal wound healing

Jabbehdari, Sayena; Yazdanpanah, Ghasem; Chen, Eric; Afsharkhamseh, Neda; Ghassemi, Mahmood; Anwar, Khandaker N.; Fonteh, Cheryl; Djalilian, Ali R.; Kang, Kai

doi:10.1007/s11033-021-06418-6

Cited by 5 publications

(4 citation statements)

References 40 publications

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“…Reins et al reported that topical 1,25 Vit D treatment (100 nM) of mouse corneas resulted in a significantly delayed rate of wound closure after both 12 and 18 h, although there was no significant difference in the total wound healing time when compared to vehicle treatment [31]. Jabbehdari et al reported that 100 nm 1,25 Vit D induced faster scratch wound closure compared with 1000 nm and 10 nm 1,25 Vit D treatment in normoglycemic mice, and a single treatment with 100 nM 1,25 Vit D significantly improved corneal wound healing compared to multiple treatments and vehicle treatment [20]. Wang et al reported that 1 nM 1,25 Vit D promoted diabetic mouse corneal wound healing [39].…”

Section: Discussionmentioning

confidence: 98%

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Effects of Topical 1,25 and 24,25 Vitamin D on Diabetic, Vitamin D Deficient and Vitamin D Receptor Knockout Mouse Corneal Wound Healing

Chen

et al. 2023

Biomolecules

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Delayed or prolonged corneal wound healing and non-healing corneas put patients at risk for ocular surface infections and subsequent stromal opacification, resulting in discomfort or visual loss. It is important to enhance corneal wound healing efficiency and quality. Vitamin D (Vit D) is both a hormone and a vitamin, and its insufficiency has been linked to immune disorders and diabetes. For this study, wound healing and recruitment of CD45+ cells into the wound area of normoglycemic and diabetic mice were examined following corneal epithelial debridement and treatment with 1,25-dihyroxyvitamin D (1,25 Vit D) or 24,25-dihydroxyvitamin D (24,25 Vit D). Treatment with topical 1,25-dihyroxyvitamin D (1,25 Vit D) resulted in significantly increased corneal wound healing rates of normoglycemic, diabetic and diabetic Vit D deficient mice. Furthermore, 24,25-dihydroxyvitamin D (24,25 Vit D) significantly increased corneal wound healing of diabetic Vit D deficient and Vit D receptor knockout (VDR KO) mice. In addition, CD45+ cell numbers were reduced in diabetic and VDR KO mouse corneas compared to normoglycemic mice, and 24,25 Vit D increased the recruitment of CD45+ cells to diabetic mouse corneas after epithelial debridement. CD45+ cells were found to infiltrate into the corneal basal epithelial layer after corneal epithelial debridement. Our data indicate that topical Vit D promotes corneal wound healing and further supports previous work that the Vit D corneal wound healing effect is not totally VDR-dependent.

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Section: Discussionmentioning

confidence: 98%

“…Vit D has been shown to contribute to corneal wound healing and epithelial integrity and to upregulate the expression of tight junctions and structural proteins [19,20]. Our group has demonstrated that Vit D deficient (VDD) diabetic mice have slower cornea epithelial wound healing than wildtype (WT) diabetic mice.…”

Section: Introductionmentioning

confidence: 99%

Effects of Topical 1,25 and 24,25 Vitamin D on Diabetic, Vitamin D Deficient and Vitamin D Receptor Knockout Mouse Corneal Wound Healing

Chen

et al. 2023

Biomolecules

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“…The topical formulation has also been used in another study by Jabbedari et al 25 who investigated the efficacy of topical 1,25 dihydroxy vitamin D in corneal wound healing using scratch assays on cultivated human corneal limbal epithelial cells and in vivo on mouse corneal epithelial debridement. Treatment with 10 −7 M 1,25 OH-vitamin D3 led to significant and rapid healing of mouse corneal epithelial wound.…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Topical Vitamin D in the Management of Dry Eye Disease Associated With Meibomian Gland Dysfunction: A Placebo-Controlled Double-Blind Randomized Controlled Trial

Hassanpour,

Langari,

Akbarzadeh

et al. 2023

Cornea

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Purpose: The aim of this study was to investigate the safety and efficacy of topical vitamin D in the management of dry eye disease associated with meibomian gland dysfunction (MGD). Methods: In this randomized controlled trial, patients with symptomatic MGD were divided into 2 groups to receive topical vitamin D drops or placebo in their randomized eyes. The exclusion criteria consisted of patients with vitamin D deficiency, previous ocular surgery, and patients with ocular diseases affecting the tear film. Patients and researchers were masked to the study groups. The outcomes included the score of Dry Eye Questionnaire (DEQ) 5 and Ocular Surface Disease Index (OSDI), corneal and conjunctival staining score, tear breakup time (TBUT), Schirmer, and MG expressibility score evaluated at baseline and weeks 4 and 8. Results: Twenty-eight eyes of 28 patients were recruited in each group. In addition to the improvement of subjective parameters in both groups, there was a statistically significantly greater improvement in the vitamin D group compared with control for average scores of OSDI (13.38 ± 7.32 vs. 27.94 ± 7.49) and DEQ5 (9.67 ± 1.86 vs. 14.14 ± 2.45) at week 8 (Ps <0.001). In addition, a significant improvement in TBUT and Schirmer test was observed in both groups in weeks 4 and 8 (P value <0.05). There was a significant difference between the treatment and control groups after 8 weeks for OSDI, DEQ5, Schirmer, TBUT, corneal fluorescein staining, and MG expressibility score (P value <0.05). Conclusions: The preliminary results of this randomized controlled trial suggested that use of topical vitamin D drops with a lipid vehicle could be safe and might significantly improve the symptoms and signs of dry eye associated with MGD.

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“…Vitamin D3 has been shown to act through ocular VDRs in several ocular pathologies. Stimulation of the VDR in respective tissues results in reduced inflammation in dry eye disease, agerelated macular degeneration (AMD), inhibition of retinal neovascularization, protection of RPE cells from oxidative damage and reduction of corneal wound scarring (37)(38)(39)(40)(41)(42)(43)(44)(45)(46). This evidence suggests that Vitamin D3 may also have the potential to modulate the VDR in the TM in order to attenuate excessive ECM deposition in the TM (47).…”

Section: Vitamin D3 and Dysregulated Ecm Remodeling In The Tmmentioning

confidence: 99%

The role of Vitamin D3 in ocular fibrosis and its therapeutic potential for the glaucomatous trabecular meshwork

Morelli-Batters¹,

Lamont²,

Elghobashy³

et al. 2022

Front. Ophthalmol.

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Glaucoma is the leading cause of irreversible blindness globally. The most prevalent subtype, Primary Open Angle Glaucoma (POAG), is characterized by increased intraocular pressure (IOP), damage to the optic nerve head and irreversible visual loss. IOP increases aqueous humor (AqH) outflow is reduced through the trabecular meshwork (TM) and Schlemm’s canal (SC). Increased outflow resistance is partly due to TM/SC dysregulation, including loss of normal trabecular meshwork cell (TMC) function, following increased levels of oxidative stress within TMC, dysregulated extracellular matrix (ECM) deposition and remodeling alongside alterations in TMC phenotype and apoptosis. Current widely available POAG treatments do not target the aberrant expression of ECM in the TM directly. As a result, most drug treatments can fail as the underlying pathological process continues unabated. Rho-kinase inhibitors have demonstrated the benefit of restoring TM/SC function, however there is a clear need to develop further treatment strategies that can target the underlying cellular processes which become dysregulated within the TMC during POAG pathogenesis. Vitamin D is suggested to be beneficial in alleviating the symptoms of fibrosis and inflammation in soft tissues. It has important functions in many major organ systems, including regulation of calcium, phosphate and parathyroid hormone. Evidence suggests that Vitamin D3 modulates ECM turnover through the conventional TGFβ-SMAD signaling, which is associated with the development of POAG. The link between Vitamin D3, inflammation and fibrosis within ocular tissues will be discussed and the potential roles of Vitamin D3 in the management of POAG patients will be explored within this review.

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Dose-dependent therapeutic effects of topical 1,25 OH-vitamin D3 on corneal wound healing

Cited by 5 publications

References 40 publications

Effects of Topical 1,25 and 24,25 Vitamin D on Diabetic, Vitamin D Deficient and Vitamin D Receptor Knockout Mouse Corneal Wound Healing

Effects of Topical 1,25 and 24,25 Vitamin D on Diabetic, Vitamin D Deficient and Vitamin D Receptor Knockout Mouse Corneal Wound Healing

Safety and Efficacy of Topical Vitamin D in the Management of Dry Eye Disease Associated With Meibomian Gland Dysfunction: A Placebo-Controlled Double-Blind Randomized Controlled Trial

The role of Vitamin D3 in ocular fibrosis and its therapeutic potential for the glaucomatous trabecular meshwork

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