Subconjunctival antisense oligonucleotides targeting TNF-α influence immunopathology and viral replication in murine HSV-1 retinitis

Abstract

After regional blockade of TNF-alpha in experimental HSV-1 retinitis TNF-alpha seems to possess an antiviral capacity against HSV-1 in the contralateral eye and participates in the immunopathology of HSV-1-induced acute retinitis.

Intravitreal treatment with antisense oligonucleotides targeting tumor necrosis factor-α in murine herpes simplex virus type 1 retinitis

“…In our previous study, the virus titers in the contralateral eye got even higher after receiving a TNF-α-ASON subconjunctival injection [15]. In contrast, TNF-α-ASON intravitreal treatment did not influence the virus replication in the eye, although it did reduce the expression of TNF-α and consecutively the retinal inflammation.…”

“…A strong fluorescent staining of TNF-α-ASON was detected in the corneal endothelium, iris, ciliary body, retinal vessels, retinal cells, and the choroid. Compared with the subconjunctival route of administration that we utilized in previous experiments [15], the staining of eye tissues was more intense after the intravitreal injection (Fig. 1).…”

“…To inoculate HSV-1, 2×10 4 plaque forming units (PFU) of HSV-1 (KOS) in 2 μl PBS were injected into the anterior chamber of the right eye [15,17].…”

“…We found that this treatment can reduce early ocular inflammatory cell infiltration. However, the virus clearance was delayed, and the severity of HSV-retinitis was even increased at later stages (day 12 PI) of the disease [15].…”

Recent Advances in Ocular Nucleic Acid-Based Therapies: The Silent Era

“…Furthermore, long-term usage of antiviral drugs can lead to development of drug-resistant viruses (90). Several authors have designed specific ASON targeting the proinflammatory cytokine tumor necrosis factor alpha (TNF) (91,92). TNF is known to possess many cell-activating and proinflammatory activities.…”