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Haydee E P Bazan, Jiucheng He, Azucena H Kakazu, Maria Soledad Cortina, Farhana Musarrat, Donna Neumann; Treatment with pigment epithelial-derived factor (PEDF) plus docosahexaenoic acid (DHA) increases corneal sensitivity and reduces inflammatory response after HSV-1 infection. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1467. doi: https://doi.org/.
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Patients with herpetic stromal keratitis (HSK) often have persistent inflammation and decreased corneal sensitivity due to damaged innervation. Loss of innervation can lead to corneal ulceration, a major clinical problem that currently has no effective therapy. Recent studies in our laboratory have shown that PEDF plus DHA treatment promotes regeneration of corneal nerves, accelerating wound healing and restoration of corneal sensitivity in experimental corneal refractive surgery. Here we used a rabbit model infected with HSV-1 to study the action of PEDF plus DHA on inflammation and sensitivity.
24 albino rabbits were bilaterally infected with HSV-1 (17 Syn+). Half of the rabbits received eye drops of PEDF+DHA three times daily, while the control group received the vehicle in the same way. At one and two weeks post-infection (pi), three animals were sacrificed from each group at each time point. Corneas were removed and fixed. Sections were cut and stained with antibodies against inflammatory cell markers CD11b+, CD4+, CD8+, neutrophil and macrophage. After two weeks, the remaining animals were treated with collagen shields containing PEDF+DHA or vehicle for seven more weeks. Corneal neovascularization, opacity and lesions were assessed by slit lamp. Corneal sensitivities were measured weekly.
One and two weeks post-infection (p.i.), vehicle-treated corneas showed a high number of inflammatory cells infiltratiion. Treatment with PEDF+DHA significantly decreased the number of inflammatory cells. Corneal lesions were also significantly decreased at day 7p.i. At day 14 corneal opacity and neovascularization were also decreased in the treated corneas. Corneal sensitivity was severely affected after infection; a recording of 0 was determined by a Cochet Bonnet aesthesiometer up to the third week. Thereafter the treated group showed a slow but steady recovery. No significant recovery of sensitivity was observed in the control group up to 9 weeks.
Treatment with PEDF+DHA can decrease inflammatory response, reduce scarring and neovascularization, and promote recovery of corneal sensitivity in a rabbit model of HSV keratitis. PEDF in combination with DHA may constitute an effective adjunctive treatment to antivirals with the potential to reduce long-term consequences of HSV corneal infection.
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