Abstract
Purpose: :
Mechanical injury and inflammation in the cornea can cause severe loss of vision and blindness. Treatment usually involves antibiotics and anti inflammatory agents, however no drug promotes corneal re-epithelialization and wound closure. Our study examines the effect of HO/05/09, a drug containing a specific PKCα inhibitor (MPDY-1), on corneal healing.
Methods: :
We have used mechanical and chemical corneal erosion models. First, erosion was performed on rabbit’s eyes (6 per group) by mechanical debridement to create central corneal erosion of 6 mm in diameter and 50 microns depth. Eyes were treated for 3 days with HO/05/09 or Balanced Salt Solution as control. In a chemically induced injury, rabbit and mice eyes were used (6 per group). Alkali burn was performed by NaOH or silver nitrate applicator stick (respectively). Eyes were treated for 7 days with HO/05/09, Strerodex & Oflox as standard of care, or left untreated.
Results: :
In the mechanical model, HO/05/09 reduced the time to full healing by 30-40%, as assessed by fluorescein staining. At 2 days post wounding, 60% of the treated wounds were fully closed versus none in the control group. 60 hours post wounding, all treated wounds exhibited full closure compared to 30% in control group. Similar results were obtained in the chemical burn models. In rabbit eyes, 2 days post wounding, 60% of wounds demonstrated 98% closure in the HO/05/09-treated group versus none in the control groups. A slit lamp morphological assessment demonstrated reduced inflammatory response of HO/05/09, as expressed by a decrease in corneal edema, conjunctival erythema and edema, and discharge. In the second model, at 7 days post wounding, 60% of mice eye’s wounds were closed in the HO/05/09 treated group, while in the control group, only 20% of the wounds reached closure. Histological analysis reveals a lower number of infiltrating cells and reduced edema in HO/05/09 treated eyes, further demonstrating the drug anti-inflammatory activity.
Conclusions: :
HO/05/09 accelerates re-epithelialization in eye injuries. It reduces inflammation and "time to heal", significantly protecting the eye from infections and prevents corneal scarring. HO/05/09 is a novel ophthalmic drug that promotes rapid and effective healing in cases such as corneal injuries and post surgical healing, and may benefit chronic conditions such as dry eye.
Keywords: cornea: epithelium • inflammation • signal transduction: pharmacology/physiology