Anti-inflammatory and anti-fibrotic effect of biomaterial and exosomes (kuragenx) in corneal ulceration model in rabbits

Abstract

Purpose : Loss of corneal transparency and poor refractive function are among the leading causes of blindness. Globally, around 200–300 million people are visually impaired, of which 5 million are affected with bilateral corneal blindness and 23 million by unilateral blindness. To address this, artificial cornea is being employed, where an injured cornea will be removed and replaced with Kuragenx (Biomaterial along with exosomes) for treatment

Methods : Corneal Ulceration Model was made in New Zealand rabbits’ cornea, by trephination followed by NaOH burn. Once the scar was formed, post 21 days of alkali injury, Kuragenx was applied. Wounded animals were divided as follow: no treatment (controls), treatment with tissue adhesive and treatment with Kuragenx. Animals were imaged using ophthalmic techniques: i) Slit-Lamp, ii) AS-OCT and iii) Pentacam, to study the corneal tissue state in live animals over a period of 3 months. Rabbits were sacrificed, eyes enucleated and further processed for histopathology, immunohistochemistry and RNA sequencing of the corneal tissue.

Results : Slit lamp revealed re-epithelization of the corneal epithelium in Kuragenx-treated rabbits, within 15 days. Central Corneal thickness of Kuragenx-treated rabbits showed central corneal thickness (380-390um) almost similar to the control. In addition, the transparency of the regenerated cornea mimicked the native cornea as measured by opacity score. Histological and Immunohistochemistry revealed reduced inflammation and fibrosis which was further validated by the RNA sequencing data where key pathways involved in fibrosis and inflammation were significantly reduced.

Conclusions : Kuragenx, a combination of biomaterial and exosomes, is a regenerative treatment, where its biomaterial part acts as a matrix for accelerating the growth of host tissue to cover the wound site and exosomes help in maintaining the anti-inflammatory and anti-fibrotic environment to accelerate the process of corneal regeneration.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.