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

Abstract

The purpose of this work was to evaluate a potentially useful animal model, Meriones shawi (M.sh)-developing metabolic X syndrome, diabetes and possessing a visual streak similar to human macula-in the study of diabetic retinopathy and diabetic macular edema (DME). Type 2 diabetes (T2D) was induced by high fat diet administration in M.sh. Body weights, blood glucose levels were monitored throughout the study. Diabetic retinal histopathology was evaluated 3 and 7 months after diabetes induction. Retinal thickness was measured, retinal cell types were labeled by immunohistochemistry and the number of stained elements were quantified. Apoptosis was determined with TUNEL assay. T2D induced progressive changes in retinal histology. A significant decrease of retinal thickness and glial reactivity was observed without an increase in apoptosis rate. Photoreceptor outer segment degeneration was evident, with a significant decrease in the number of all cones and M-cone subtype, but-surprisingly-an increase in S-cones. Damage of the pigment epithelium was also confirmed. A decrease in the number and labeling intensity of parvalbumin- and calretinin-positive amacrine cells and a loss of ganglion cells was detected. Other cell types showed no evident alterations. No DME-like condition was noticed even after 7 months. M.sh could be a useful model to study the evolution of diabetic retinal pathology and to identify the role of hypertension and dyslipidemia in the development of the reported alterations. Longer follow up would be needed to evaluate the potential use of the visual streak in modeling human macular diseases.

Detailed Evaluation of Possible Ganglion Cell Loss in the Retina of Zucker Diabetic Fatty (ZDF) Rats

“…Even within the same model – like in ZDF rats used in the present study – controversial data has been published. Some reported an increase in the number of apoptotic cells already in 19 week-old ZDF rats 48 while in another report on 23 week-old animals by Johnson and co-workers 25 and also in a previous work of our group on 32 week-old rats 56 no cell loss was observed. The reason behind this discrepancy is currently unknown but due to its huge potential impact on diagnosis and therapy it calls for further studies.…”

“…Immunocytochemistry is probably the most sensitive and adequately selective method for identifying RGCs. Due to their diverse subtypes, all antibodies available to date label only a portion, some of them even the vast majority of the RGC population but never all RGCs 56 . There are also evident differences in sensitivity and labelling characteristics between the antibodies available.…”

“…Quantification of RGCs may be performed on sections as well as on whole retinas or retinal pieces with plenty of examples for each technique in literature available 56 . The sampling method may be especially important in the central retinal regions, where RGC are not evenly distributed but are grouped into rows, with the regions of axon bundles and bigger vessels completely free of perikarya.…”

Interphotoreceptor Retinoid-Binding Protein Implications in Diabetic Retinopathy

“…Interestingly, the foveal cones appear to be mostly affected revealing a loss of approximately 30% of the M-cones 7 weeks after type 2 diabetes was induced in the animals [46]. Studies in rats also have shown alterations in the photoreceptor outer segments with the S-cones and the M-cones most severely affected [47].…”

The Use of Optical Coherence Tomography for the Detection of Early Diabetic Retinopathy

“…Also, damage to the pigment epithelium was shown with a loss of ganglion cells. Other retinal cell types showed no evident alterations [12].…”