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Jelena Potic, Martial Mbefo, Michael Nicolas, Yvan Arsenijevic; An in vitro model of human retina detachment reveals a common death mechanism with other models of retinal dystrophies. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2259.
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© ARVO (1962-2015); The Authors (2016-present)
We previously identified that cell cycle proteins are reactivated in various rodent models of inherited retinal dystrophies as well as during light damage. Moreover, cyclin-dependent kinases (CDKs) are common actors in these models and play a crucial role in the execution phase of photoreceptor death (Zencak et al., 2013). In this study, we investigated whether such mechanism is also involved in an in vitro model of human retinal detachment (RD) which was shown to activate different pathways during the initiation of photoreceptor degeneration.
Human retinas were obtained through eye globe donation for research purposes. The peripheral retina was cut in different pieces and cultivated on Millipore membrane as explant. Cell death was studied between retina with (control, group 1) and without retinal pigment epithelium cells (RPE) to mimic RD (group 2). The tissue was studied at different time points (24h and 7 days) and histological analyses for TUNEL and CDKs expression were performed.
The number of TUNEL positive cells, compared between 24h and 7 days, increased with time in retina with (1.5+/-0.6 to 6+/-1.6) and without RPE (3.8+/-0.3 to 41+/-7.2). TUNEL positive cells were significantly more present in RD model after 7 days of incubation in comparison to the control group (41 vs 6, P<0.001),.. CDK4-positive cells, were expressed in both groups but significantly higher in group 2 at 24h (0.7+/-0.2 vs 1.3+/-0.2, P=0.04) and at 7 DIV (0.8+/-0.3 vs 3.7+/-0.6, P=0.007). Other cell cycle proteins are under analyses.
CDK4 is expressed in an in vitro model of RD of human retinas. These first observations are suggesting possible overlapping mechanisms of cell death characterized in animal models of retinal degeneration. The results of this study are opening new fields of research and are moving us on next step on testing anti-CDK inhibitors on this in vitro model of human retina.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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