Study of retinal neurodegeneration and maculopathy in diabetic : A particular animal model with human‐like maculaMeriones shawi: A particular animal model with human‐like macula

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Diabetic retinopathy (DR) is a serious complication of diabetes mellitus and a leading cause of preventable vision loss (Gangwani, Lian, McGhee, Wong, & Li, 2016; Lee, Wong, & Sabanayagam, 2015; Nentwich & Ulbig, 2015; Sayin, Kara, & Pekel, 2015; Stewart, 2016). DR has long been regarded as a vascular disease characterized by hemorrhage, exudates, loss of pericytes, the appearance of acellular capillaries, microaneurysms, a breakdown of the blood‐retinal barrier and neovascularization (Antonetti, Klein, & Gardner, 2012). Now, it is acknowledged that DR is a neurovascular disease in which neurodegenerative changes occur earlier than clinically detectable vascular alterations (Simo, Hernandez, & European Consortium for the Early Treatment of Diabetic, 2012).
Several functional, cellular and molecular studies (Barber et al., 1998; Bearse, Han, Schneck, & Adams, 2004; Fletcher, Phipps, Ward, Puthussery, & Wilkinson‐Berka, 2007; Kizawa, Machida, Kobayashi, Gotoh, & Kurosaka, 2006; Lieth et al., 1998; Ola, Nawaz, Khan, & Alhomida, 2013; Ozawa et al., 2011; Saidi et al., 2011) on diabetic patients and experimental animal models, have shown neural damages early after the onset of diabetes preceding any sign of vasculopathy. Apoptosis of retinal ganglion cells (Barber et al., 1998), cholinergic and dopaminergic amacrine cells (Gastinger, Singh, & Barber, 2006), loss of photoreceptors (Park et al., 2003), the degeneration of the outer segments of rods and cones (Enzsoly et al., 2014), and damage of the retinal pigment epithelium and AII amacrine cells (Enzsoly et al., 2015) has been reported. Neural apoptosis is accompanied also by reactive changes in glial cells with increased expression of GFAP (glial fibrillary acidic protein; Mizutani, Gerhardinger, & Lorenzi, 1998) and microglia activation (Rungger‐Brandle, Dosso, & Leuenberger, 2000; Zeng, Ng, & Ling, 2000).
Early neuroglial alterations of DR were elucidated in different rodents in which hyperglycemia occurs either spontaneously or is induced by chemical agents or surgical operation (Engerman, 1976; Jiang, Yang, & Luo, 2015; Jo, Cho, Kim, Jun, & Kim, 2013; Lai & Lo, 2013; Saidi et al., 2011). Indeed, these validated animals were established to improve our knowledge about the mechanisms of the pathogenesis and in order to develop valuable treatments for this disease. However, none of these animal models mimic exactly the human pathology and they have limitations (Jo et al., 2013; Lai & Lo, 2013; Robinson, Barathi, Chaurasia, Wong, & Kern, 2012), hence the need to keep searching for the appropriate animal model.
Settaf et al. (2000) have demonstrated that Meriones shawi (M.sh) is a new potential model to study the metabolic X syndrome since this animal spontaneously develops obesity, glucose intolerance, type 2 diabetes (T2D), dyslipidemia, and hypertension. M.sh has also been used in several further studies to analyze diabetic complications and possible therapeutic interventions (Aissaoui, Zizi, Israili, & Lyoussi, 2011; Benhaddou‐Andaloussi et al., 2011; Berrougui et al., 2003). Furthermore, this species (Hammoum et al., 2017) and another member of the same family, Meriones ungiculatus (Huber et al., 2010) has a prominent visual streak similar to the human macula with outstandingly high cell densities and the lack of major blood vessels in the area (Figure 1). This macula‐like region would make this model especially interesting and valuable to study diabetic retinal complications and diabetic macular edema (DME) specifically, since the other frequently used rodents (rats and mice) do not possess this central region. DME is characterized by excessive vasopermeability and edematous damage and has been considered as the major cause of blindness in diabetes (Joussen, Smyth, & Niessen, 2007).
Previously, we published the first description of neuroglial alterations in the retina after 3 months of diabetes induction in M.
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