Abstract
Purpose: :
To characterize a porcine model of experimental choroidal neovascularization (CNV) induced by subretinal injection of Matrigel matrix, a solubilized basement membrane preparation rich in extracellular matrix proteins, and to evaluate the effects of CNV on the morphology of the overlying retina.
Methods: :
Ten female Yorkshire Cross pigs (6–8 wk of age) were treated according to the ARVO resolution for the use of animals in research. Under anesthesia, pars plana vitrectomy was performed in the right eye of each pig. Two to four small sub–retinal blebs were created in the posterior pole of the experimental eye by subretinal injection of growth factor reduced Matrigel (BD Biosciences) diluted with PBS (study blebs) or PBS solution alone (control blebs) with purposeful punctuate rupture of Bruch’s membrane at injection. Development of CNV was monitored using fluorescein angiography and fundus photography. At 1, 2, 4, and 8 wk post–surgery, pigs (n= 2 or more per time point) were anesthetized, and their eyes were enucleated, fixed in paraformaldehyde, paraffin embedded and processed for histological analysis. Serial transverse sections were collected throughout the blebs, and overall morphology was examined in hematoxylin stained sections. Evidence of neurodegenerative changes in the neurosensory retina, specifically at the photoreceptor synapse, were analyzed immunohistochemically.
Results: :
One animal was excluded from the study due to retinal detachment. Fluorescein angiography failed to detect CNV on days 3 and 4. However from day 7 onward, early lacy hyperfluorescence and late leakage typical of "classic" CNV was observed in study blebs. Growth of CNV progressed over the following 4 to 8 wk. The presence of CNV was confirmed in analysis of light micrographs, as was progressive retinal degeneration, including photoreceptor loss and synaptic degeneration.
Conclusions: :
The subretinal injection of a combination of extracellular matrix proteins produces a model of classic CNV in a pig eye, with overlying retinal degeneration. This model may be useful for evaluation of potential drug treatments and surgical techniques on CNV and is significant since porcine eyes share greater similarity to human eyes in size and scleral thickness as compared to the commonly used rodent eye.
Keywords: choroid: neovascularization • retinal degenerations: cell biology • vitreoretinal surgery