Research Article: Electroretinographic evidence suggesting that the type 2 diabetic retinopathy of the sand rat Psammomys obesus is comparable to that of humans

Date Published: February 8, 2018

Publisher: Public Library of Science

Author(s): Ahmed Dellaa, Maha Benlarbi, Imane Hammoum, Nouha Gammoudi, Mohamed Dogui, Riadh Messaoud, Rached Azaiz, Ridha Charfeddine, Moncef Khairallah, Pierre Lachapelle, Rafika Ben Chaouacha-Chekir, Radouil Tzekov.

http://doi.org/10.1371/journal.pone.0192400

Abstract

Type 2 diabetic retinopathy is the main cause of acquired blindness in adults. The aim of this work was to examine the retinal function of the sand rat Psammomys obesus as an animal model of diet-induced type 2 diabetes when subjected to a hypercaloric regimen.

Hyperglycemia was induced in Psammomys obesus by high caloric diet (4 kcal/g). The visual function of control (n = 7) and diabetic (n = 7) adult rodents were followed up during 28 consecutive weeks with full-field electroretinogram(ERG) recordings evoked to flashes of white light according to the standard protocol of the International Society for Clinical Electrophysiology of Vision protocol (ISCEV).

Twenty-eight weeks following the induction of diabetes, results revealed significantly reduced and delayed photopic and scotopic ERG responses in diabetic rats compared to control rats. More specifically, we noted a significant decrease in the amplitude of the dark-adapted 0.01ERG (62%), a- and b-wave amplitudes of the dark-adapted 3.0 ERG (33.6%, 55.1%) and the four major oscillatory potentials components (OP1-OP4) (39.0%, 75.2%, 54.8% and 53.7% respectively). In photopic conditions, diabetic rats showed a significant decrease in a- and b-wave (30.4%, 43.4%), photopic negative response (55.3%), 30 Hz flicker (63.7%), OP1-OP4(51.6%, 61.8%, 68.3% and 47.5% respectively) and S-cone (34.7%). Significantly delayed implicit times were observed for all ERG components in the diabetic animals. Results obtained are comparable to those characterizing the retinal function of patients affected with advanced stage of diabetic retinopathy.

Psammomys obesus is a useful translational model to study the pathophysiology of diabetic retinopathy in order to explore new therapeutic avenues in human patients.

Partial Text

Diabetic retinopathy (DR), which can lead to blindness in severe cases, is reported to affect more than 90% of diabetic patients [1]. The pathophysiology of diabetic retinopathy is believed to result from the sustained exposure to hyperglycemia which leads to retinal biochemical abnormalities [2]. In addition, although DR has long been recognized as a vascular disease [3–5], the neuronal cells of the retina are also affected [6–10]. Supportive of the latter, previous studies reported that some visual anomalies such as color vision deficits [11, 12] or decreased contrast sensitivity [13] precede the vascular signs of DR, suggesting that the vascular abnormalities may not be the first sign characterizing the onset of DR [14, 15]. Similarly, it was previously shown that flash and multifocal electroretinograms can detect retinal neurosensory changes long before an observable retinopathy occurs [16–18]. For instance, it was shown that the onset of the proliferative phase of diabetic retinopathy was better predicted with the selective amplitude reduction of the oscillatory potentials of the ERG than with the vascular lesions seen in fundus photographs [19, 20]. Clinical studies have also shown that retinal ganglion cells (RGC) and neuronal activity progressively decreases with advancing DR as indicated by the photopic negative response (PhNR) that follows the photopic ERG b-wave [14]. Chemically-induced diabetes was also shown to yield early functional changes in the retina, such as in streptozotocin (STZ)-treated rodents [21–24] and alloxan-treated rabbits [25, 26].

P.obesus maintained on a high-fat diet for 28 consecutive weeks developed hyperglycemia with body weight increase as reported in a previous study of ours [31]. This high-fat diet induced a metabolic stress syndrome in P.obesus which led to an alteration to the retinal structure [31]. The present study demonstrated that this alteration to the retinal structure is paralleled by an equally profound deterioration in retinal function (decrease in amplitude scotopic and photopic a- and b-waves, OP1-OP4 components, PhNR, Flicker and S-cone).

The present study clearly demonstrated for the first time that long-lasting and significant alterations in visual function detected by full-field ERG take place after 28 weeks of diet-induced type 2 diabetes in the retina of the sand rat. Thus, the diabetic sand rat appears to be an animal model that mimics several important features of the human form of diabetic retinopathy.

 

Source:

http://doi.org/10.1371/journal.pone.0192400

 

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