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Maria Soledad Cortina, Jiucheng He, Neumann Donna, Farhana Musarrat, Azucena H Kakazu, Haydee E P Bazan; Pigment epithelial derived factor (PEDF) plus docosahexaenoic acid (DHA) induce a dual response of the immune system and increase nerve regeneration in HSV-1-infected corneas. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3075.
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© ARVO (1962-2015); The Authors (2016-present)
HSV-1 infection is a major cause of corneal blindness in the USA. Associated complications include persistent inflammation and neurotrophic keratitis. Studies using a rabbit model infected with HSV-1 and treated with PEDF+DHA have shown increased corneal sensitivity and reduced inflammation (ARVO 2014). Here we investigate the inflammatory-immune response during the first two weeks of primary HSV infection and the cornea nerve density and presence of lymphocytes in the trigeminal ganglion (TG) during viral latency.
Rabbits were inoculated with 100,000 pfu/eye of HSV-1 17 Syn+ strain. Twenty-four hours post inoculation (p.i.), treatment with PEDF+DHA or vehicle was started. Animals were divided into 3 groups, and euthanized at 7, 14 days and 12 weeks. Corneas from the first two groups were stained with antibodies against CD8+, CD4+, CD11b, F40/8 and neutrophils. The number of cells with positive staining was recorded for each group. In the third group, corneal sensitivity was measured every week with a Cochet Bonet esthesiometer. Corneas and trigeminal ganglia (TG) were removed and corneal specimens were stained with βII-neurotubulin antibody and TG with CD8+ antibody.
At one week p.i., there was a very significant increase in lymphocytes, macrophages and neutrophil infiltration in the rabbits treated with PEDF+DHA that was reverted at 2 weeks. Corneal lesions were significantly decreased in the PEDF+DHA group at 14 days. No corneal sensation was detected in rabbits treated with vehicle for 12 weeks; however, corneal sensitivity started to recover by week 3 in the PEDF+DHA-treated rabbits. After 12 weeks p.i., corneal nerve density was increased in the PEDF+DHA group, and the TG of the rabbits contained CD8+ cells surrounding the axons.
The innate immune-inflammatory response is enhanced by PEDF+DHA treatment during the early phase of viral infection, probably to increase HSV-1 clearance from the cornea. This immune modulation is likely to mediate, at least in part, the decrease in corneal lesions, recovery of sensitivity and nerve regeneration observed with treatment. The presence of CD8+ lymphocytes In the TG has the potential to inhibit virus reactivation and suggests a protective role of PEDF+DHA against recurrent disease.
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