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Santiago Delgado-Tirado, Dhanesh Amarnani, Leo A Kim, Joseph F. Arboleda-Velasquez; An in-vivo model of proliferative vitreoretinopathy by intravitreal injection of cells from human-derived PVR membranes in rabbits.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4219.
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© ARVO (1962-2015); The Authors (2016-present)
Proliferative vitreoretinopathy (PVR) is a sight-threatening condition that remains without an effective treatment. The aim of this study is to develop and characterize an experimental model of PVR in rabbits that could be used for drug testing using human-derived cells injection and to compare it with ARPE-19 cell line injection model.
PVR membranes were obtained from human donors who had PVR grade C undergoing surgery. PVR membrane cells were isolated and primary cultured (C-PVR). Study animals were divided into two groups; one injected with C-PVR cells and other with ARPE-19 cells. Male and female New Zealand White rabbits (n=12) of 6 to 8-weeks of age were subjected to C3F8 gas vitrectomy (0.3 ml). Three days later, gas was removed and cells were injected intravitreally over the optic nerve area (C-PVR or ARPE-19 cells in 0.1ml ≈800,000 cells). Animals were examined by indirect ophthalmoscopy and optical coherence tomography after cell injection and at 1, 2 and 4 weeks post injection. PVR grade of severity was classified according to level of proliferation, size, number and extension of intravitreal membranes and presence of focal traction or retinal detachment (RD).
All animals developed signs of PVR. After time-course characterization, C-PVR group showed an early onset of PVR signs and faster progression rate compared to ARPE-19 group, one day after cell injection and after 1 week. However, after 2 weeks, PVR severity was similar between both groups. PVR features progressed with time and increased in severity. Most common findings identified were formation of vitreous floaters, vitreous strands, intravitreal membranes, and retrolental proliferation. No focal traction or RD were identified.
Our results showed C-PVR in-vivo model as a promising model that resembles in a more accurate fashion the cell environment needed to develop PVR. Unlike ARPE-19, C-PVR are primary cultures and include multiple cell types relevant to the disease, which is more characteristic of the human condition and may lead to models more predictive of clinical efficacy. C-PVR works at least equal to ARPE19 cells in a PVR model in rabbits. In future studies, we will examine whether increasing cell number and longer periods of observation increase severity of PVR including retinal traction or detachment.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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