June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Topical application of anti-miR-183/96/182 cluster causes transient, reversible corneal nerve reduction and demonstrates therapeutic potential against bacterial keratitis
Author Affiliations & Notes
  • Naman Gupta
    Ophthalmology, Visual and anatomical sciences, Wayne State University, Detroit, Michigan, United States
  • Sharon A McClellan
    Ophthalmology, Visual and anatomical sciences, Wayne State University, Detroit, Michigan, United States
  • Denise Bessert
    Ophthalmology, Visual and anatomical sciences, Wayne State University, Detroit, Michigan, United States
  • Linda D Hazlett
    Ophthalmology, Visual and anatomical sciences, Wayne State University, Detroit, Michigan, United States
  • Shunbin Xu
    Ophthalmology, Visual and anatomical sciences, Wayne State University, Detroit, Michigan, United States
  • Footnotes
    Commercial Relationships   Naman Gupta None; Sharon McClellan None; Denise Bessert None; Linda Hazlett None; Shunbin Xu None
  • Footnotes
    Support  NIH grants R01EY02605902; R01EY016058 and P30EY004068; a Research to Prevent Blindness unrestricted grant to the Department of Ophthalmology, Visual and Anatomical Science, Wayne State University School of Medicine.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4274. doi:
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    • Get Citation

      Naman Gupta, Sharon A McClellan, Denise Bessert, Linda D Hazlett, Shunbin Xu; Topical application of anti-miR-183/96/182 cluster causes transient, reversible corneal nerve reduction and demonstrates therapeutic potential against bacterial keratitis. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4274.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Previously we identified that the miR-183/96/182 cluster (miR-183C) modulates corneal response to Pseudomonas aeruginosa (PA) infection by regulating corneal nerve function and innate immunity1-3.Local application of anti-miR-183C in a prophylactic regimen causes a transient, reversible reduction of corneal nerve density and protects against PA keratitis4. This study is to test whether topical application of anti-miR-183C alone in a therapeutic regimen has similar effects on corneal nerves and PA keratitis.

Methods : 8 weeks old, female C57BL/6 mice were used. Under anesthesia, the cornea of the left eye was scarified by three 1-mm incisions using a 25 5/8-gauge needle. 5.0 × 106 CFU PA (strain 19660; ATCC) in 5 μl was topically delivered. Six or 24 hours after infection and twice daily thereafter, 5 μl of anti-miR-183C or negative-control oligoribonucleotides (NC ORN) in sterile saline (8 μM/each) was topically applied to the infected cornea for 5 days. To test the effect of anti-miR-183C alone on corneal nerves, anti-miR-183C or NC ORNs were topically applied to the cornea 24 hours after a mock infection and twice daily thereafter. At 5 days post (mock) infection (dpi), immunofluorescence (IF) of flat-mounted corneas with bIII-tubulin antibody was done and corneal nerve density was determined.

Results : Topical application of anti-miR-183C resulted in a significant reduction of corneal nerve density. To test whether anti-miR-183C-induced reduction of corneal nerves causes permanent changes to corneal nerves, after the last topical application, another group of anti-miR-treated mice were held for another week without any treatment. Our result showed that their nerve density was fully recovered. Preliminary data on PA-infected corneas showed that topical application of anti-miR-183C significantly reduced the severity of the disease at 3 dpi (p<0.05); at 5 dpi, anti-miR-183C treated eyes had slightly decreased severity, however, didn’t pass the statistical threshold (p=0.09).

Conclusions : Topical application of anti-miR-183C causes transient and reversible corneal nerve density reduction and has a therapeutic potential against PA keratitis. Further studies to optimize the treatment regimen and uncover the molecular mechanisms of the therapeutic effect are warranted.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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