Abstract
Purpose :
There are currently no large-mammal surgical models for geographic atrophy with choroidal neovascularization (CNV). Our goal was to develop a porcine surgical RPE (retina pigment epithelium) debridement model to study the time course of photoreceptor cell loss and choroidal remodeling. This model was developed to study the therapeutic potential of RPE sheet transplantation, delivered using erodible fibrin scaffolds in mitigating the effects of acquired RPE cell loss.
Methods :
This research is compliant with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Six 2-month-old female domestic pigs (Sus scrofa domesticus), purpose-bred for medical research were used for this study. Animals were screened for overall health by a veterinarian and underwent pre-surgical ophthalmological examination to assure that the cornea and lens were clear and that there was no evidence of retinal dialysis or detachment in the operative eye. Three-port triamcinolone-assisted 25-gauge pars plana vitrectomy was performed with careful separation of the posterior hyaloid in the area centralis. A 41-gauge needle was used to create a retinal bleb, detaching the area centralis outside of the tapetum. Endodiathermy was applied along the proximal bleb and a 2mm retinotomy was created with vertical scissors. A nitinol wire or 5-0 proline loop was used to gently debride and remove a 5mm diameter region RPE cells without rupturing Bruch’s membrane. Fluid-air exchange was performed and 20% SF6 gas was injected. Animals underwent color fundus photos at 2 weeks post-op. Fundus photos, OCT and OCT angiography (OCTA) were also performed at 1,2,3,4 and 6 months post-op. Retinal histology was obtained at 2, 4 and 6 months, post-op.
Results :
Debridement of RPE resulted in geographic atrophy with progressive loss of photoreceptors and rapid loss of choriocapillaris within 2 months in all eyes. Pachychoroidal changes were also observed in Sattler and Haller layers. OCTA revealed non-exudative type 1 CNV, initially at the edges of the debridement zone by 2 months. At six months, non-exudative filamentous type 1 CNV progressed toward the center of the debridement zone.
Conclusions :
Surgical debridement of the RPE results in geographic atrophy and CNV, reproducing both forms of advanced AMD. This surgical model is useful as a means of testing the role of RPE and other cell replacement in treating advanced AMD.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.