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Akos Lukats, Klaudia Szabo, Anna Enzsoly, Arnold Szabo, Agoston Szel, Bulcsu Dekany, Gabor Mark Somfai, Kornelia Lenke Laurik, Tamas Radovits, Csaba Matyas, Rozina Ida Hajdu; Detailed quantitative and qualitative evaluation of potential ganglion cell pathology in the retina of Zucker Diabetic Fatty (ZDF) Rats. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3222.
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© ARVO (1962-2015); The Authors (2016-present)
Literature data indicates that in diabetes neural retinal degeneration exists prior to clinically detectable vasculopathy. As one of the first morphologic signs of this, clinical studies are showing the thinning of the ganglion cell layer (GCL) in vivo in human diabetic patents. In contrast, results of animal models on ganglion cell pathology are contradictory. The aim of the present study was to give a detailed evaluation of the ganglion cell numbers, distribution patterns and to evaluate the potential changes in morphology and staining characteristics of neural cells in the GCL.
32 week-old Zucker Diabetic Fatty (ZDF) rats, a type 2 diabetes model were used in this study. Ganglion cells were labeled on whole mounted retinas by immunohistochemistry using Brn3a, NeuN and RBPMS antibodies. The complete retina was photographed and the number of ganglion cells were counted in 80±14 sample fields across the retina. Isodensity maps were constructed and analyzed. Retinal thickness and the number of apoptotic cells were determined on vertical cryosections. The morphology, number and staining characteristics of neurons of the GCL were also examined. Statistical analysis were performed by Mann-Whitney U test.
There was no significant difference in mean ganglion cell densities (1418±171 in controls vs. 1646±49 cells/mm2 in diabetic specimen) and the distribution patterns were also comparable in the two groups. In line with this, we detected no decrease in retinal thickness and no increase in the number of apoptotic cells in the GCL (1.38±1.54 cells/section in control vs.1.26±1.24 in diabetic specimen). Neural elements of the GCL were analyzed with more than 15 different antibodies. Although changes in morphology and staining characteristics were evident for some antibodies, no decrease in the number of any population was detectable.
Our results clearly indicate that there is no major ganglion cell loss even after more than 20 weeks of onstanding, untreated diabetes in ZDF rats. This contradicts some previous studies in animal models and underlines the importance of using whole retinas and not sections for GCL counts. Also, the possibility that factors other than ganglion cell loss (eg. remodeling of dendrites in the inner plexiform layers) should also be considered as a potential explanation for GCL thinning on clinical examinations.
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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