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Delay of corneal epithelial wound healing and induction of keratocyte apoptosis by platelet-activating factor.
Invest Ophthalmol Vis Sci. 2002 May; 43(5):1422-8.IO

Abstract

PURPOSE

To examine the role of the lipid mediator platelet-activating factor (PAF) in epithelial wound healing.

METHODS

A 7-mm central de-epithelializing wound was produced in rabbit corneas, and the tissue was incubated with 125 nM carbamyl PAF (cPAF), an analogue of PAF. Rabbit corneal epithelial and stromal cells were also cultured in the presence of cPAF. Cell adhesion, proliferation, and migration assays were conducted. Apoptosis was assayed by TUNEL staining on preparations of corneal tissue sections and in cells in culture.

RESULTS

Twenty-four hours after injury, 50% of the wounded area was covered by new epithelium, whereas only 30% was covered in the presence of cPAF. At 48 hours, the epithelium completely closed the wound, but only 45% of the original wound was covered in corneas treated with cPAF. Similar inhibition of epithelial wound closure was found with human corneas incubated with PAF in organ culture. Moreover, addition of several growth factors involved in corneal wound healing, such as epidermal growth factor, hepatocyte growth factor, and keratinocyte growth factor, could not overcome the inhibitory action of PAF in wound closure. Three PAF antagonists, BN50727, BN50730, and BN50739, abolished the effect of PAF. A significant increase in TUNEL-positive staining occurred in corneal stromal cells (keratocytes), which was inhibited by preincubating the corneas with PAF antagonists. However, no TUNEL-positive staining was found in epithelial cells. TUNEL-staining results in cultured stromal cells (keratocytes) and epithelial cells in first-passage cell culture were similar to those in organ-cultured corneas. In addition, PAF caused 35% to 56% inhibition of adhesion of epithelial cells to proteins of the extracellular matrix: collagen I and IV, fibronectin, and laminin. There were no significant changes in proliferation or migration of epithelial cells induced by the lipid mediator.

CONCLUSIONS

The results suggest PAF plays an important role in preventing corneal wound healing by affecting adhesion of epithelial cells and increasing apoptosis in stromal cells. PAF antagonists could be of therapeutic importance during prolonged ocular inflammation, helping to avoid loss of corneal transparency and visual acuity.

Authors+Show Affiliations

Department of Ophthalmology, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, LA 70112, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11980856

Citation

Chandrasekher, Gudiseva, et al. "Delay of Corneal Epithelial Wound Healing and Induction of Keratocyte Apoptosis By Platelet-activating Factor." Investigative Ophthalmology & Visual Science, vol. 43, no. 5, 2002, pp. 1422-8.
Chandrasekher G, Ma X, Lallier TE, et al. Delay of corneal epithelial wound healing and induction of keratocyte apoptosis by platelet-activating factor. Invest Ophthalmol Vis Sci. 2002;43(5):1422-8.
Chandrasekher, G., Ma, X., Lallier, T. E., & Bazan, H. E. (2002). Delay of corneal epithelial wound healing and induction of keratocyte apoptosis by platelet-activating factor. Investigative Ophthalmology & Visual Science, 43(5), 1422-8.
Chandrasekher G, et al. Delay of Corneal Epithelial Wound Healing and Induction of Keratocyte Apoptosis By Platelet-activating Factor. Invest Ophthalmol Vis Sci. 2002;43(5):1422-8. PubMed PMID: 11980856.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Delay of corneal epithelial wound healing and induction of keratocyte apoptosis by platelet-activating factor. AU - Chandrasekher,Gudiseva, AU - Ma,Xiang, AU - Lallier,Thomas E, AU - Bazan,Haydee E P, PY - 2002/5/1/pubmed PY - 2002/6/4/medline PY - 2002/5/1/entrez SP - 1422 EP - 8 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 43 IS - 5 N2 - PURPOSE: To examine the role of the lipid mediator platelet-activating factor (PAF) in epithelial wound healing. METHODS: A 7-mm central de-epithelializing wound was produced in rabbit corneas, and the tissue was incubated with 125 nM carbamyl PAF (cPAF), an analogue of PAF. Rabbit corneal epithelial and stromal cells were also cultured in the presence of cPAF. Cell adhesion, proliferation, and migration assays were conducted. Apoptosis was assayed by TUNEL staining on preparations of corneal tissue sections and in cells in culture. RESULTS: Twenty-four hours after injury, 50% of the wounded area was covered by new epithelium, whereas only 30% was covered in the presence of cPAF. At 48 hours, the epithelium completely closed the wound, but only 45% of the original wound was covered in corneas treated with cPAF. Similar inhibition of epithelial wound closure was found with human corneas incubated with PAF in organ culture. Moreover, addition of several growth factors involved in corneal wound healing, such as epidermal growth factor, hepatocyte growth factor, and keratinocyte growth factor, could not overcome the inhibitory action of PAF in wound closure. Three PAF antagonists, BN50727, BN50730, and BN50739, abolished the effect of PAF. A significant increase in TUNEL-positive staining occurred in corneal stromal cells (keratocytes), which was inhibited by preincubating the corneas with PAF antagonists. However, no TUNEL-positive staining was found in epithelial cells. TUNEL-staining results in cultured stromal cells (keratocytes) and epithelial cells in first-passage cell culture were similar to those in organ-cultured corneas. In addition, PAF caused 35% to 56% inhibition of adhesion of epithelial cells to proteins of the extracellular matrix: collagen I and IV, fibronectin, and laminin. There were no significant changes in proliferation or migration of epithelial cells induced by the lipid mediator. CONCLUSIONS: The results suggest PAF plays an important role in preventing corneal wound healing by affecting adhesion of epithelial cells and increasing apoptosis in stromal cells. PAF antagonists could be of therapeutic importance during prolonged ocular inflammation, helping to avoid loss of corneal transparency and visual acuity. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/11980856/Delay_of_corneal_epithelial_wound_healing_and_induction_of_keratocyte_apoptosis_by_platelet_activating_factor_ L2 - https://iovs.arvojournals.org/article.aspx?volume=43&issue=5&page=1422 DB - PRIME DP - Unbound Medicine ER -