Abstract
Purpose :
Annually close to 40,000 patients suffering from corneal endothelia cell (CEnC) dystrophy or dysfunction undergo corneal transplantation in the US. The endogenous ligand of MC1R, a-MSH, protects CEnC from stress and injury in various preclinical models. To demonstrate efficacy of the newly synthesized MC1R agonist K173, we assessed its effect on corneal stromal edema and wound closure using a surgical Descement-only stripping (DSO) model in rabbits.
Methods :
For the surgical DSO challenge model, a 5mm circular area of the Descemet’s membrane was first scored using a reverse Terry-Sinskey hook, then peeled along with the CEnC from the overlying stroma and removed using forceps. The incision site was closed with 9-0 nylon suture, BSS was injected to normalize the intraocular pressure. After an initial dose ranging period on the day of challenge, rabbit eyes were dosed once daily starting on Day 8 of the study, with 0.5, 0.1, and 0.05 mg/mL formulations along with a vehicle control. Animals were monitored by weekly ocular exams and OCT, followed by tissue collection for IHC upon study termination.
Results :
As quantified by OCT measures, treatment with 0.1 mg/mL of K173 resulted in a dramatic and significant reduction on corneal stromal thickness after 1 week (day 15 of study) of dosing and remained low for the duration of the study. The 0.05 mg/ml group also showed a significant decrease in stromal edema after 2 weeks of dosing. At study conclusion, a subset of corneas (n=3) was collected and assessed for wound closure. While treatment did enhance wound closure, statistical analysis could not be performed due to the small sample size.
Conclusions :
Topical administration of our novel MC1R agonist is efficacious in this rabbit DSO model by significantly reducing stromal edema and enhancing CEnC wound healing. These data establish K173 as a potential superior and non-invasive treatment option for early to mid-stage patients affected by CEnC dysfunction.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.