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Published on: June 14, 2021
Early Choriocapillaris Loss in a Porcine Model of RPE Cell Debridement Precedes Pathology That Simulates Advanced
Raymond Iezzi1, Brittni A Scruggs1, Jarel Gandhi1
1Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States.
Purpose:
No large-mammal surgical models exist for geographic atrophy (GA), choroidal neovascularization (CNV), and pachychoroidal vascular remodeling. Our goal was to develop a porcine RPE debridement model of advanced macular degeneration to study photoreceptor cell loss and choroidal remodeling.
Methods:
Seven 2-month-old female domestic pigs were used for this study. After 25G vitrectomy, the area centralis was detached via subretinal bleb. A nitinol wire (Finesse Flex Loop) was used to debride RPE cells across a 3- to 5-mm diameter region. Fluid-air exchange was performed, and 20% SF6 gas injected. Animals underwent fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT-angiography (OCTA) at 2 weeks, 1 month, 2 months, 3 months, and 6 months postoperatively. Retinal histology was obtained at euthanasia, 2 months (n = 3), 3 months (n = 2), or 6 months (n = 2) after surgery.
Results:
RPE debridement resulted in GA with rapid loss of choriocapillaris, progressive loss of photoreceptors, and pachychoroidal changes in Sattler's and Haller's layers in all seven eyes undergoing debridement within 2 months. OCT and histological findings included subretinal disciform scar with overlying outer retinal atrophy; outer retinal tubulations and subretinal hyper-reflective material. OCTA revealed type 2 CNV (n = 4) at the edges of the debridement zone by 2 months, but there was no significant exudation noted at any time point.
Conclusions:
Surgical debridement of the RPE results in GA, CNV, and pachychoroid and reproduced all forms of advanced macular degeneration. This surgical model may be useful in examining the role of RPE and other cell replacement in treating advanced macular disease.
Insights
A new porcine surgical model effectively replicates advanced macular degeneration, including geographic atrophy (GA) and choroidal neovascularization (CNV). This model aids research into RPE cell replacement therapies for macular diseases.
Area of Science:
- Ophthalmology
- Retinal Diseases
- Surgical Models
Background:
- Current large-mammal models are lacking for geographic atrophy (GA), choroidal neovascularization (CNV), and pachychoroidal vascular remodeling.
- Advanced macular degeneration encompasses a spectrum of retinal pathologies with significant visual impact.
Purpose of the Study:
- To develop a novel porcine surgical model simulating key features of advanced macular degeneration.
- To investigate photoreceptor cell loss and choroidal remodeling in a large-mammal setting.
Main Methods:
- A surgical RPE debridement technique was employed in seven pigs following vitrectomy.
- Imaging modalities including OCT and OCTA, alongside histological analysis, were used for evaluation.
- Animals were monitored for up to six months post-surgery.
Main Results:
- RPE debridement successfully induced GA, choriocapillaris loss, photoreceptor degeneration, and pachychoroidal changes within two months.
- Optical coherence tomography revealed outer retinal atrophy and subretinal hyper-reflective material.
- Choroidal neovascularization (CNV) was observed in four eyes at the debridement zone's periphery.
Conclusions:
- Surgical RPE debridement in pigs creates a robust model for GA, CNV, and pachychoroid, mimicking advanced macular degeneration.
- This model offers a valuable platform for evaluating cell replacement therapies and understanding disease mechanisms.
